Overview: What is a Metal?
This blog post is going to be focused on the metal, beryllium. Before we dive in, we are gonna go over some basic knowledge of metal toxicity. Metals are the oldest known toxin to humans. Metals are unique toxins in that they cannot be created or destroyed by humans but we can alter the chemical structure of metals which changes that toxic potential of that particular metal.
Most metals are widely distributed in the environment and the common route of exposure is inhalation or ingestion. Factors that impact metal toxicity include age at time of exposure, gender, and capacity for bio transformation. This is important, especially when the the individual exposed is a child. With this brief background, lets dive into Beryllium.
Beryllium Basic Facts:
- Beryllium is found in about 30 different mineral species. The most important are beryl (beryllium aluminium silicate) and bertrandite (beryllium silicate). Emerald and aquamarine are precious forms of beryl.
Uses:
- Beryllium is used in alloys with copper or nickel to make gyroscopes, springs, electrical contacts, spot-welding electrodes and non-sparking tools. Mixing beryllium with these metals increases their electrical and thermal conductivity.
- Other beryllium alloys are used as structural materials for high-speed aircraft, missiles, spacecraft and communication satellites.
- Beryllium is relatively transparent to X-rays so ultra-thin beryllium foil is finding use in X-ray lithography. Beryllium is also used in nuclear reactors as a reflector or moderator of neutrons.
Common manifestation of Beryllium Poisoning:
- Berylliosis-Beryllium sensitivity (BeS)
- Acute Beryllium Disease-rare in clinical practice
- Chronic Beryllium Disease (CBD)-Scarring of lung tissue. individuals are usually sensitized to berllium before reaching the point of developing CBD.
- Lung Cancer
Toxicokinetics of Beryllium
Link to image on the right is here!! Toxicity is similar to Sarcoidosis. Look at image under Mechanism of action!
Biotransformation:
- Beryllium acts as a major histocompatability complex (MHC) class II restricted antigen that stimulates the proliferation and accumulation of beryllium-specific CD4+ T cells in the lungs
Mechanism of Action:
- CD4+ T lymphocytes recognize beryllium as an antigen that triggers cell proliferation and release of cytokines and inflammatory mediators.
- The release of inflammatory mediators results in an accumulation of mononuclear-cell infiltrates and fibrosis that lead to the lesion typical of the disease—a noncaseating granuloma.
Link to image on the right is here!
Target Organs:
- Lungs and Immune system
Signs and Symptoms
- Early stage of the disease-there are no present symptoms
- Swelling and scarring of the lungs-due to CD4+ T lymphocytes accumulating in fluid
- Difficulty breathing
- weakness and fatigue
- weight loss
Carcinogenicity
- Beryllium and its compounds are classified as Group 1, carcinogenic to humans by The International Agency for Research on Cancer
- The U.S. Environmental Protection Agency classifies inhaled beryllium in Group B1, a probably human carcinogen.
- Epidemiological studies have shown an increased risk of lung cancer among beryllium-exposed workers and among workers with acute and CBD. The excess incidence of lung cancer was more pronounced among those with acute beryllium disease than among those with CBD.
- Increased lung cancer among workers with higher beryllium exposures and lack of evidence for confounding by cigarette smoking, provide further evidence that beryllium is a human lung carcinogen
Genetic susceptibility
- Development of CBD appears to depend not only on the history of exposure to beryllium but on the genotype and phenotype of the person exposed.
- Variants in the HLA-DPβ1 domain in CBD remains the best-studied and strongest genetic association in this CBD.
Treatment of Beryllium Poisoning
Care Options
- There is currently no cure for CBD. Treatment of symptoms is possible.
- Avoid further beryllium exposure
- Prednisone- corticosteriod used to decrease inflammation.
- Methotrexate- used for those not responding to steroid treatment.
Link to image on the right is HERE!
Hope you enjoyed this week’s post on Beryllium! If you are interested in this topic! Here is a nice video I found on YouTube that explains the mechanism more clearly!
References:
- https://www.rsc.org/periodic-table/element/4/beryllium
- Newman, L S et al. “The natural history of beryllium sensitization and chronic beryllium disease.” Environmental health perspectives vol. 104 Suppl 5,Suppl 5 (1996): 937-43. doi:10.1289/ehp.96104s5937
- National Research Council (US) Committee on Beryllium Alloy Exposures; National Research Council (US) Committee on Toxicology. Managing Health Effects of Beryllium Exposure. Washington (DC): National Academies Press (US); 2008. 4, Mechanisms, Genetic Factors, and Animal Models of Chronic Beryllium Disease. Available from: https://www.ncbi.nlm.nih.gov/books/NBK214768/
- https://my.clevelandclinic.org/health/diseases/13807-beryllium-disease
- https://www.atsdr.cdc.gov/csem/csem.asp?csem=5&po=8#:~:text=Carcinogenic%20Effects&text=The%20International%20Agency%20for%20Research,human%20carcinogen%20(IRIS%202002).