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Journal of Immunology (Baltimore, Md. :... Jan 2016Chronic beryllium (Be) disease is a granulomatous lung disorder that results from Be exposure in a genetically susceptible host. The disease is characterized by the... (Review)
Review
Chronic beryllium (Be) disease is a granulomatous lung disorder that results from Be exposure in a genetically susceptible host. The disease is characterized by the accumulation of Be-responsive CD4(+) T cells in the lung, and genetic susceptibility is primarily linked to HLA-DPB1 alleles possessing a glutamic acid at position 69 of the β-chain. Recent structural analysis of a Be-specific TCR interacting with a Be-loaded HLA-DP2-peptide complex revealed that Be is coordinated by amino acid residues derived from the HLA-DP2 β-chain and peptide and showed that the TCR does not directly interact with the Be(2+) cation. Rather, the TCR recognizes a modified HLA-DP2-peptide complex with charge and conformational changes. Collectively, these findings provide a structural basis for the development of this occupational lung disease through the ability of Be to induce posttranslational modifications in preexisting HLA-DP2-peptide complexes, resulting in the creation of neoantigens.
Topics: Berylliosis; Beryllium; CD4-Positive T-Lymphocytes; Genetic Predisposition to Disease; HLA-DP beta-Chains; Humans; Hypersensitivity; Lung; Protein Processing, Post-Translational; Receptors, Antigen, T-Cell
PubMed: 26685315
DOI: 10.4049/jimmunol.1502011 -
International Journal of Environmental... Jan 2010Beryllium is a lightweight metal with unique qualities related to stiffness, corrosion resistance, and conductivity. While there are many useful applications,... (Review)
Review
Beryllium is a lightweight metal with unique qualities related to stiffness, corrosion resistance, and conductivity. While there are many useful applications, researchers in the 1930s and 1940s linked beryllium exposure to a progressive occupational lung disease. Acute beryllium disease is a pulmonary irritant response to high exposure levels, whereas chronic beryllium disease (CBD) typically results from a hypersensitivity response to lower exposure levels. A blood test, the beryllium lymphocyte proliferation test (BeLPT), was an important advance in identifying individuals who are sensitized to beryllium (BeS) and thus at risk for developing CBD. While there is no true "gold standard" for BeS, basic epidemiologic concepts have been used to advance our understanding of the different screening algorithms.
Topics: Berylliosis; Beryllium; Humans; Models, Theoretical; Probability Theory
PubMed: 20195436
DOI: 10.3390/ijerph7010115 -
American Journal of Respiratory Cell... Jan 2019
Topics: Beryllium; DNA Methylation; Epigenesis, Genetic; Humans; Lung; Lung Diseases
PubMed: 30321053
DOI: 10.1165/rcmb.2018-0306ED -
Journal of Synchrotron Radiation May 2022High-quality bi-concave 2D focusing diamond X-ray lenses of apex-radius R = 100 µm produced via laser-ablation and improved via mechanical polishing are presented...
High-quality bi-concave 2D focusing diamond X-ray lenses of apex-radius R = 100 µm produced via laser-ablation and improved via mechanical polishing are presented here. Both for polished and unpolished individual lenses and for stacks of ten lenses, the remaining figure errors determined using X-ray speckle tracking are shown and these results are compared with those of commercial R = 50 µm beryllium lenses that have similar focusing strength and physical aperture. For two stacks of ten diamond lenses (polished and unpolished) and a stack of eleven beryllium lenses, this paper presents measured 2D beam profiles out of focus and wire scans to obtain the beam size in the focal plane. These results are complemented with small-angle X-ray scattering (SAXS) measurements of a polished and an unpolished diamond lens. Again, this is compared with the SAXS of a beryllium lens. The polished X-ray lenses show similar figure errors to commercially available beryllium lenses. While the beam size in the focal plane is comparable to that of the beryllium lenses, the SAXS signal of the polished diamond lenses is considerably lower.
PubMed: 35510996
DOI: 10.1107/S1600577522001795 -
Toxicology and Applied Pharmacology Nov 2022Besides smoking, lung cancer can be caused by other factors, including heavy metals such as cadmium, nickel, arsenic, beryllium and hexavalent chromium [Cr(VI)], which... (Review)
Review
Besides smoking, lung cancer can be caused by other factors, including heavy metals such as cadmium, nickel, arsenic, beryllium and hexavalent chromium [Cr(VI)], which is used in multiple settings, resulting in widespread environmental and occupational exposures as well as heavy use. The mechanism by which Cr(VI) causes lung cancer is not completely understood. Currently, it is admitted chromosome instability is a key process in the mechanism of Cr(VI)-induced cancer, and previous studies have suggested Cr(VI) impacts the lung tissue in mice by triggering tissue damage and inflammation. However, the mechanism underlying Cr(VI)-induced inflammation and its exact role in lung cancer are unclear. Therefore, this review aimed to systematically examine previous studies assessing Cr(VI)-induced inflammation and to summarize the major inflammatory pathways involved in Cr(VI)-induced inflammation. In cell culture studies, COX2, VEGF, JAK-STAT, leukotriene B4 (LTB4), MAPK, NF-ҡB and Nrf2 signaling pathways were consistently upregulated by Cr(VI), clearly demonstrating that these pathways are involved in Cr(VI)-induced inflammation. In addition, Akt signaling was also shown to contribute to Cr(VI)-induced inflammation, although discrepant findings were reported. Few mechanistic studies were performed in animal models, in which Cr(VI) upregulated oxidative pathways, NF-kB signaling and the MAPK pathway in the lung tissue. Similar to cell culture studies, opposite effects of Cr(VI) on Akt signaling were reported. This work provides insights into the mechanisms by which Cr(VI) induces lung inflammation. However, discrepant findings and other major issues in study design, both in cell and animal models, suggest that further studies are required to unveil the mechanism of Cr(VI)-induced inflammation and its role in lung cancer.
Topics: Animals; Mice; Arsenic; Beryllium; Cadmium; Chromium; Cyclooxygenase 2; Inflammation; Leukotriene B4; Lung; Lung Neoplasms; NF-E2-Related Factor 2; NF-kappa B; Nickel; Proto-Oncogene Proteins c-akt; Vascular Endothelial Growth Factor A
PubMed: 36208701
DOI: 10.1016/j.taap.2022.116265 -
The Annals of Occupational Hygiene Jan 2011Beryllium metal was classified in Europe collectively with beryllium compounds, e.g. soluble salts. Toxicological equivalence was assumed despite greatly differing... (Review)
Review
Beryllium metal was classified in Europe collectively with beryllium compounds, e.g. soluble salts. Toxicological equivalence was assumed despite greatly differing physicochemical properties. Following introduction of the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation, beryllium metal was classified as individual substance and more investigational efforts to appropriately characterize beryllium metal as a specific substance apart from soluble beryllium compounds was required. A literature search on toxicity of beryllium metal was conducted, and the resulting literature compiled together with the results of a recently performed study package into a comprehensive data set. Testing performed under Organisation for Economic Co-Operation and Development guidelines and Good Laboratory Practice concluded that beryllium metal was neither a skin irritant, an eye irritant, a skin sensitizer nor evoked any clinical signs of acute oral toxicity; discrepancies between the current legal classification of beryllium metal in the European Union (EU) and the experimental results were identified. Furthermore, genotoxicity and carcinogenicity were discussed in the context of the literature data and the new experimental data. It was concluded that beryllium metal is unlikely to be a classical nonthreshold mutagen. Effects on DNA repair and morphological cell transformation were observed but need further investigation to evaluate their relevance in vivo. Animal carcinogenicity studies deliver evidence of carcinogenicity in the rat; however, lung overload may be a species-specific confounding factor in the existing studies, and studies in other species do not give convincing evidence of carcinogenicity. Epidemiology has been intensively discussed over the last years and has the problem that the studies base on the same US beryllium production population and do not distinguish between metal and soluble compounds. It is noted that the correlation between beryllium exposure and carcinogenicity, even including the soluble compounds, remains under discussion in the scientific community and active research is continuing.
Topics: Animals; Beryllium; Carcinogens; Cell Transformation, Neoplastic; Environmental Exposure; European Union; Humans; Occupational Exposure; Rats
PubMed: 21196456
DOI: 10.1093/annhyg/meq073 -
IARC Monographs on the Evaluation of... 1993
Topics: Animals; Beryllium; Carcinogens; Glass; Humans; Industry; Neoplasms; Occupational Diseases; Occupational Exposure
PubMed: 8022058
DOI: No ID Found -
Toxicology Letters May 2022Dermal exposure to hazardous substances such as chemicals, toxics, metallic items and other contaminants may present substantial danger for health. Beryllium (Be) is a...
Dermal exposure to hazardous substances such as chemicals, toxics, metallic items and other contaminants may present substantial danger for health. Beryllium (Be) is a hazardous metal, especially when inhaled and/or in direct contact with the skin, associated with chronic beryllium disease (CBD) and Be sensitization (BeS). The objective of this study was to investigate the percutaneous penetration of beryllium and copper contained in metallic items as eyeglass temple tips (specifically BrushCAST® Copper Beryllium Casting Alloys containing Be 0.35 < 2.85%; Cu 95.3-98.7%), using Franz diffusion cells. This work demonstrated that the total skin absorption of Cu was higher (8.86%) compared to Be (4.89%), which was expected based on the high percentage of Cu contained in the eyeglass temple tips. However, Be accumulated significantly in the epidermis and dermis (up to 0.461 µg/cm) and, to a lesser extent, in the stratum corneum (up to 0.130 µg/cm) with a flux of permeation of 3.52 ± 4.5 µg/cm/hour and lag time of 2.3 ± 1.3 h, after cutaneous exposure of temple tip into 1.0 mL artificial sweat for 24 h. Our study highlights the importance of avoiding the use of Be alloys in items following long-term skin contact.
Topics: Alloys; Berylliosis; Beryllium; Copper; Eyeglasses; Humans
PubMed: 35427767
DOI: 10.1016/j.toxlet.2022.04.001 -
Federal Register Jan 2017The Occupational Safety and Health Administration (OSHA) is amending its existing standards for occupational exposure to beryllium and beryllium compounds. OSHA has...
The Occupational Safety and Health Administration (OSHA) is amending its existing standards for occupational exposure to beryllium and beryllium compounds. OSHA has determined that employees exposed to beryllium at the previous permissible exposure limits face a significant risk of material impairment to their health. The evidence in the record for this rulemaking indicates that workers exposed to beryllium are at increased risk of developing chronic beryllium disease and lung cancer. This final rule establishes new permissible exposure limits of 0.2 micrograms of beryllium per cubic meter of air (0.2 [mu]g/m\3\) as an 8-hour time-weighted average and 2.0 [mu]g/m\3\ as a short-term exposure limit determined over a sampling period of 15 minutes. It also includes other provisions to protect employees, such as requirements for exposure assessment, methods for controlling exposure, respiratory protection, personal protective clothing and equipment, housekeeping, medical surveillance, hazard communication, and recordkeeping. OSHA is issuing three separate standards--for general industry, for shipyards, and for construction--in order to tailor requirements to the circumstances found in these sectors.
Topics: Berylliosis; Beryllium; Humans; Occupational Exposure; Occupational Health; Protective Clothing; Respiratory Protective Devices; United States; United States Occupational Safety and Health Administration
PubMed: 28071878
DOI: No ID Found -
Cancer Medicine Dec 2016We aimed at investigating mortality among beryllium-exposed workers, according to solubility of beryllium and beryllium compounds. We conducted an historical cohort...
We aimed at investigating mortality among beryllium-exposed workers, according to solubility of beryllium and beryllium compounds. We conducted an historical cohort study of 16,115 workers employed during 1925-2008 in 15 facilities, including eight entailing exposure to insoluble beryllium and seven entailing exposure to soluble/mixed beryllium compounds, who were followed up for mortality until 2011. Data were analyzed using indirect standardization and Cox regression modeling. Lung cancer standardized mortality ratio (SMR, national reference rates) was 1.02 (95% confidence interval [CI]: 0.94-1.10) in the whole cohort, 0.88 (95% CI: 0.75-1.03) in the insoluble beryllium subcohort, and 1.09 (95% CI: 0.99-1.09) in the soluble/mixed beryllium subcohort. For lung cancer, there was an association with period of hire in soluble/mixed beryllium plants but not in insoluble plants, and, conversely, employment in soluble/mixed plants was associated with increased mortality only among workers hired before 1955. There was no trend with duration of employment. Mortality from chronic beryllium disease increased, in particular, among workers hired before 1955 in soluble/mixed beryllium facilities. There was no increase in lung cancer mortality in the entire cohort and lung cancer mortality was not increased among beryllium workers hired in 1955 or later in soluble/mixed beryllium facilities, or at any time among those employed in insoluble beryllium facilities.
Topics: Berylliosis; Beryllium; Cause of Death; Humans; Male; Mortality; Occupational Exposure; Proportional Hazards Models; Public Health Surveillance; Risk Factors; Time Factors
PubMed: 27766788
DOI: 10.1002/cam4.918