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Beryllium
Beryllium SC Gad, Gad Consulting Services, Cary, NC, USA Ó 2014 Elsevier Inc. All rights reserved.
l
Chemical Abstracts Service Registry Number: 7440-41-7 Synonyms: Glucinum, Glucinium l Valence States: 0, þ2 l
Background Although known through the mineral beryl, Be3Al2(SiO3)6, for millennia, beryllium was discovered as an element in 1797 by Louis-Nicolas Vauquelin, although it was not isolated as a metal until Friedrich Wöhler and Antoine Bussy independently succeeded in this venture independently by reacting potassium metal with beryllium chloride in a platinum crucible, yielding beryllium metal and potassium chloride. Its use in metallurgy and electrical components were largely developed in the 1920s.
Uses Beryllium is an important industrial metal because of its material properties; that is, it is lighter than aluminum and six times stronger than steel. Often alloyed with other metals such as copper, beryllium is a key component of materials used in the aerospace and electronics industries. Beryllium has a small neutron cross-section, which makes it useful in the production of nuclear weapons and in sealed neutron sources. Specifically, beryllium is used in nuclear reactors as a neutron reflector or moderator, and in the aerospace industry in inertial guidance systems; beryllium alloys (consisting of copper or aluminum) are also used in structural material. Beryllium oxide is used as an additive in glass, ceramics, and plastics and as a catalyst in organic reactions. In the past, beryllium was widely used in the manufacture of fluorescent lights and neon signs. Alloyed with copper, aluminum, or nickel, beryllium imparts excellent electrical and thermal conductivity.
Environmental Fate and Behavior Beryllium enters the environment principally through emissions from the combustion of fossil fuels and ore processing. Average ambient air concentrations in the United States have been measured at 0.03 ng m3, whereas median concentration in cities is 0.2 ng m3. Insolubility of beryllium and many of its compounds can lead to long-term persistence in the environment, as particulates suspended in water until deposition in sediment, or in soils. Concentrations of beryllium in soil are found in the United States, as well as, more recently, in Brazil, Argentina, Madagascar, India, and Russia. Long-range transport of beryllium is common in continental river systems, whereas brackish mixing zones exhibit scavenging. It is not yet known whether beryllium ceases
Encyclopedia of Toxicology, Volume 1
transport in these estuarine waters and deposits in sediments, or continues to the deep ocean, although beryllium concentrations in deep ocean waters around the world are uniform. A measured bioconcentration factor (BCF) of 19 was reported for beryllium in bluegill fish. Other investigators have reported a BCF of 100 for freshwater and marine plants, invertebrates, and fish. Chemicals with BCFs <1000 will not bioaccumulate significantly in aquatic organisms. It is possible that bottom-feeding crustaceans, such as clams and oysters, could accumulate beryllium from sediment and show higher bioconcentration than freshwater fish. No evidence for significant biomagnification of beryllium within food chains was found.
Exposure and Exposure Monitoring The primary exposure pathway for beryllium is inhalation. Inhalation, ingestion, and dermal contact are possible exposure pathways in workplace settings. Exposure to small amounts of beryllium occurs with ingestion of some foods and drinking water. Beryllium enters the air, water, and soil as a result of natural and human activities. Emissions from burning coal and oil increase beryllium levels in air. Beryllium enters waterways from the wearing away of rocks and soil. Most of the synthetic beryllium that enters waterways comes when industry dumps wastewater and when beryllium dust in the air from industrial activities settles over water. Beryllium, as a chemical component, occurs naturally in soil; however, disposal of coal ash, incinerator ash, and industrial wastes may increase the concentration of beryllium in soil. In air, beryllium compounds are present mostly as fine dust particles. The dust eventually settles over land and water.
Toxicokinetics Beryllium is not well absorbed by any route. Oral absorption of beryllium is <0.01% and probably only occurs in the acidic stomach environment. About half of inhaled beryllium is cleared in w2 weeks. The remainder is cleared slowly and the residual becomes fixed in the lung (granulomata). The half-life of beryllium in rat blood is w3 h. Beryllium is distributed to all tissues. High doses generally go to the liver and then are gradually transferred to the bone. Most beryllium concentrates in the skeleton. Beryllium is excreted in the urine; however, the fraction of administered dose excreted in urine is variable.
Mechanism of Toxicity Beryllium compromises the immune system. Enzymes catalyzed by magnesium or calcium can be inhibited by beryllium; succinic dehydrogenase is activated. Beryllium exposure
http://dx.doi.org/10.1016/B978-0-12-386454-3.00820-4
435
436
Beryllium
leads to a deficiency in lung carbon monoxide diffusing capacity. Hypercalcemia (excess of calcium in the blood) can occur.
Acute and Short-Term Toxicity (or Exposure) Animal The pulmonary effects of inhaled beryllium have been evaluated in a variety of laboratory animal species. Monkeys, for example, exposed to relatively high concentrations of beryllium compounds developed symptoms and histopathological findings consistent with acute beryllium disease.
Immunotoxicity Beryllium exerts several important immunotoxic effects, including induction of a beryllium-antigen specific adaptive immune response and the triggering of inflammatory and innate immune responses. Genetic susceptibility plays a role in CBD adaptive immune responses, mainly mediated through single nucleotide polymorphisms in HLA-DP and, to a lesser extent, HLA-DR. The adaptive response is characterized by influx and proliferation of CD4þ central and effector memory T cells expressing Th1 cytokines. Insights into the immunopathogenesis of CBD have implications for the understanding of other immune-mediated granulomatous disorders and for metal antigen behavior.
Human The major toxicological effects of beryllium are on the lung. Acute exposure to soluble beryllium compounds (e.g., fluoride, an intermediate in the ore extraction process) irritates the entire respiratory tract, may produce acute chemical pneumonitis, and can result in fatal pulmonary edema. Hypersensitivity, which appears to be mediated by the immune system, may also occur following exposure. This means that future exposure to beryllium may produce health effects at concentrations lower than those generally associated with the effect (the individual becomes much more sensitive to beryllium). The acute disease in humans is also marked by conjunctivitis, nasopharyngitis, tracheobronchitis, and dermatitis.
Chronic Toxicity (or Exposure) Animal Although beryllium produces cancer in more than one animal species (lung cancer in rats and monkeys; osteogenic sarcoma in rabbits), it does not appear to be teratogenic.
Human Chronic exposure to insoluble beryllium compounds, particularly the oxides, leads to berylliosis (a chronic granulomatous disease), which begins with a cough and chest pains. In most cases, these symptoms soon lead to pulmonary dysfunction. The latency period ranges from months to 25 years. Diagnosis based on clinical, radiographic, and lung function evidence has been found to be difficult. Other effects of beryllium exposure include enlargement of the heart (which can lead to congestive heart failure), enlargement of the liver, and kidney stones. Finger ‘clubbing’ is often seen with berylliosis. Skin lesions are the most common industrial exposure symptom. Three distinct skin lesions have been noted following exposure to beryllium: dermatitis, ulceration, and granulomas. There appears to be an immunological component to chronic beryllium disease, including the dermal responses. Although available information from epidemiological studies is insufficient to confirm human carcinogenesis, the data strongly suggest beryllium is associated with cancer in humans, and it is categorized as a B1 (probable human carcinogen) by the US Environmental Protection Agency (EPA).
Reproductive Toxicity Little data are available on the reproductive effects of beryllium. Large acute doses have had no effect on reproduction, although continued administration during pregnancy has led to death in utero and quickly after birth. It has also been reported that rats exposed to low levels of beryllium have an increased number of litters.
Genotoxicity Beryllium’s genotoxicity is not entirely clear, owing to weak and/or inconsistent evidence from studies, but there is sufficient evidence to consider it a weak genotoxin. In vitro studies indicate that beryllium induces morphological transformations in mammalian cells, but beryllium is not mutagenic in bacterial systems. There are studies that have exhibited chromosome aberrations in human lymphocytes, as well as increased sister chromatid exchange (SCE).
Carcinogenicity The American Conference of Governmental Industrial Hygienists (ACGIH) classifies beryllium as group TLV-1 (a substance that causes cancer in humans). The DFG maintains the same classification as the ACGIH, although the group is referred to as MAK 1. Also, the IARC classifies it as group 1 (sufficient evidence for carcinogenicity in humans). US EPA classification of beryllium is as groups B1, probable human carcinogen, limited evidence from epidemiological studies, and L, meaning likely to produce cancer in humans. There are several studies suggesting that occupational exposure to beryllium, largely in the form of dust, increases incidence of lung cancer, especially in individuals after recovery from acute beryllium pneumonitis.
Clinical Management Treatment of the acute disease includes bed rest, oxygen therapy, mechanical ventilation when needed, and corticosteroids. Chelation has been used to treat beryllium toxicity; however, no one agent is recommended over another. Aurin tricarboxylic acid has been used to protect primates from beryllium overdose, but human trials have not been conducted.
Beryllium
437
Ecotoxicology
Further Reading
Fish do not accumulate beryllium from water into their bodies to any great extent. A major portion of beryllium in soil does not dissolve in water but remains bound to soil, so it is not very likely to move deeper into the ground and enter groundwater. In the environment, chemical reactions can change the water-soluble beryllium compounds into insoluble forms. In some cases, water-insoluble beryllium compounds can change to soluble forms. Exposure to water-soluble beryllium compounds in the environment, in general, pose a greater threat to human health than water-insoluble forms. No evidence was found to substantiate that biomethylation or any other environmental process results in the volatilization of beryllium into the atmosphere from water or soil. Beryllium is extremely toxic to warm water fish in soft water. The degree of toxicity decreases with increasing water hardness. Bioconcentration of beryllium in fish to high levels is not likely because of the low uptake of beryllium from water by aquatic animals.
Bingham, E., Cohrssen, B., Powell, C.H. (Eds.), 2001. Patty’s Toxicology, fifth ed. John Wiley & Sons, Inc., New York. Gordon, T., Bowser, D., 2003. Beryllium: genotoxicity and carcinogenicity. Mutat. Res. 533, 99–105. Jakubowski, M., Dalezymski, C., 2009. Beryllium. In: Nordberg, G.F., Fowler, B.A., Nordberg, M., Friberg, L.T. (Eds.), Handbook on the Toxicology of Metals, third ed. Elsevier, New York, pp. 416–432. Kreiss, K., 2011. Beryllium: a paradigm for occupational lung disease and its prevention. Occup. Environ. Med. 68 (11), 787–788. Kriebel, D., Brain, J.D., Sprince, N.L., Kazemi, H., 1988. The pulmonary toxicity of beryllium. Am. Rev. Respir. Dis. 137, 464–473. Muller, C., Salehi, F., Mazer, B., Bouchard, M., Adam-Poupart, A., Chevalier, G., Truchon, G., Lambert, J., Zayed, J., 2011 October. Immunotoxicity of 3 chemical forms of beryllium following inhalation exposure. Int. J. Toxicol. 30 (5), 538–545. Nordberg, G.F., Fowler, B.A., Nordberg, M., Friberg, L.T., 2007. Handbook on the Toxicology of Metals, third ed. Associated Press, London. Taylor, T.P., Ding, M., Ehler, D.S., et al., 2003. Beryllium in the environment: a review. J. Environ. Sci. Health A Environ. Sci. Eng. Toxic Hazard. Subst. Control 38, 439–469. Williams, W.J., 1988. Beryllium disease. Postgrad. Med. J. 64, 511–516.
Other Hazards
Relevant Websites
Exposure Standards and Guidelines The ACGIH threshold limit value, 8-h time-weighted average is 0.002 mg m3 for beryllium and beryllium compounds.
Miscellaneous Emeralds are a beryllium compound, beryl, Be3Al2(SiO3)6, which is colored green by the presence of trace quantities of chromium or vanadium.
See also: Metals; Respiratory Tract Toxicology.
http://www.epa.gov/ttn/atw/hlthef/berylliu.html - US Environmental Protection Agency, Air Toxics website: Beryllium Compounds http://minerals.usgs.gov/minerals/pubs/commodity/beryllium/ - US Geological Survey, Minerals Information: Beryllium http://www.cdc.gov/niosh/topics/beryllium/ - Centers for Disease Control, Workplace Safety and Health Topics: Beryllium http://toxnet.nlm.nih.gov/ - Toxnet homepage, search for ‘beryllium’. http://www.epa.gov/iris/toxreviews/0012tr.pdf - US Environmental Protection Agency, Toxicity review of Beryllium.
l
Chemical Abstracts Service Registry Number: 7440-41-7 Synonyms: Glucinum, Glucinium l Valence States: 0, þ2 l
Background Although known through the mineral beryl, Be3Al2(SiO3)6, for millennia, beryllium was discovered as an element in 1797 by Louis-Nicolas Vauquelin, although it was not isolated as a metal until Friedrich Wöhler and Antoine Bussy independently succeeded in this venture independently by reacting potassium metal with beryllium chloride in a platinum crucible, yielding beryllium metal and potassium chloride. Its use in metallurgy and electrical components were largely developed in the 1920s.
Uses Beryllium is an important industrial metal because of its material properties; that is, it is lighter than aluminum and six times stronger than steel. Often alloyed with other metals such as copper, beryllium is a key component of materials used in the aerospace and electronics industries. Beryllium has a small neutron cross-section, which makes it useful in the production of nuclear weapons and in sealed neutron sources. Specifically, beryllium is used in nuclear reactors as a neutron reflector or moderator, and in the aerospace industry in inertial guidance systems; beryllium alloys (consisting of copper or aluminum) are also used in structural material. Beryllium oxide is used as an additive in glass, ceramics, and plastics and as a catalyst in organic reactions. In the past, beryllium was widely used in the manufacture of fluorescent lights and neon signs. Alloyed with copper, aluminum, or nickel, beryllium imparts excellent electrical and thermal conductivity.
Environmental Fate and Behavior Beryllium enters the environment principally through emissions from the combustion of fossil fuels and ore processing. Average ambient air concentrations in the United States have been measured at 0.03 ng m3, whereas median concentration in cities is 0.2 ng m3. Insolubility of beryllium and many of its compounds can lead to long-term persistence in the environment, as particulates suspended in water until deposition in sediment, or in soils. Concentrations of beryllium in soil are found in the United States, as well as, more recently, in Brazil, Argentina, Madagascar, India, and Russia. Long-range transport of beryllium is common in continental river systems, whereas brackish mixing zones exhibit scavenging. It is not yet known whether beryllium ceases
Encyclopedia of Toxicology, Volume 1
transport in these estuarine waters and deposits in sediments, or continues to the deep ocean, although beryllium concentrations in deep ocean waters around the world are uniform. A measured bioconcentration factor (BCF) of 19 was reported for beryllium in bluegill fish. Other investigators have reported a BCF of 100 for freshwater and marine plants, invertebrates, and fish. Chemicals with BCFs <1000 will not bioaccumulate significantly in aquatic organisms. It is possible that bottom-feeding crustaceans, such as clams and oysters, could accumulate beryllium from sediment and show higher bioconcentration than freshwater fish. No evidence for significant biomagnification of beryllium within food chains was found.
Exposure and Exposure Monitoring The primary exposure pathway for beryllium is inhalation. Inhalation, ingestion, and dermal contact are possible exposure pathways in workplace settings. Exposure to small amounts of beryllium occurs with ingestion of some foods and drinking water. Beryllium enters the air, water, and soil as a result of natural and human activities. Emissions from burning coal and oil increase beryllium levels in air. Beryllium enters waterways from the wearing away of rocks and soil. Most of the synthetic beryllium that enters waterways comes when industry dumps wastewater and when beryllium dust in the air from industrial activities settles over water. Beryllium, as a chemical component, occurs naturally in soil; however, disposal of coal ash, incinerator ash, and industrial wastes may increase the concentration of beryllium in soil. In air, beryllium compounds are present mostly as fine dust particles. The dust eventually settles over land and water.
Toxicokinetics Beryllium is not well absorbed by any route. Oral absorption of beryllium is <0.01% and probably only occurs in the acidic stomach environment. About half of inhaled beryllium is cleared in w2 weeks. The remainder is cleared slowly and the residual becomes fixed in the lung (granulomata). The half-life of beryllium in rat blood is w3 h. Beryllium is distributed to all tissues. High doses generally go to the liver and then are gradually transferred to the bone. Most beryllium concentrates in the skeleton. Beryllium is excreted in the urine; however, the fraction of administered dose excreted in urine is variable.
Mechanism of Toxicity Beryllium compromises the immune system. Enzymes catalyzed by magnesium or calcium can be inhibited by beryllium; succinic dehydrogenase is activated. Beryllium exposure
http://dx.doi.org/10.1016/B978-0-12-386454-3.00820-4
435
436
Beryllium
leads to a deficiency in lung carbon monoxide diffusing capacity. Hypercalcemia (excess of calcium in the blood) can occur.
Acute and Short-Term Toxicity (or Exposure) Animal The pulmonary effects of inhaled beryllium have been evaluated in a variety of laboratory animal species. Monkeys, for example, exposed to relatively high concentrations of beryllium compounds developed symptoms and histopathological findings consistent with acute beryllium disease.
Immunotoxicity Beryllium exerts several important immunotoxic effects, including induction of a beryllium-antigen specific adaptive immune response and the triggering of inflammatory and innate immune responses. Genetic susceptibility plays a role in CBD adaptive immune responses, mainly mediated through single nucleotide polymorphisms in HLA-DP and, to a lesser extent, HLA-DR. The adaptive response is characterized by influx and proliferation of CD4þ central and effector memory T cells expressing Th1 cytokines. Insights into the immunopathogenesis of CBD have implications for the understanding of other immune-mediated granulomatous disorders and for metal antigen behavior.
Human The major toxicological effects of beryllium are on the lung. Acute exposure to soluble beryllium compounds (e.g., fluoride, an intermediate in the ore extraction process) irritates the entire respiratory tract, may produce acute chemical pneumonitis, and can result in fatal pulmonary edema. Hypersensitivity, which appears to be mediated by the immune system, may also occur following exposure. This means that future exposure to beryllium may produce health effects at concentrations lower than those generally associated with the effect (the individual becomes much more sensitive to beryllium). The acute disease in humans is also marked by conjunctivitis, nasopharyngitis, tracheobronchitis, and dermatitis.
Chronic Toxicity (or Exposure) Animal Although beryllium produces cancer in more than one animal species (lung cancer in rats and monkeys; osteogenic sarcoma in rabbits), it does not appear to be teratogenic.
Human Chronic exposure to insoluble beryllium compounds, particularly the oxides, leads to berylliosis (a chronic granulomatous disease), which begins with a cough and chest pains. In most cases, these symptoms soon lead to pulmonary dysfunction. The latency period ranges from months to 25 years. Diagnosis based on clinical, radiographic, and lung function evidence has been found to be difficult. Other effects of beryllium exposure include enlargement of the heart (which can lead to congestive heart failure), enlargement of the liver, and kidney stones. Finger ‘clubbing’ is often seen with berylliosis. Skin lesions are the most common industrial exposure symptom. Three distinct skin lesions have been noted following exposure to beryllium: dermatitis, ulceration, and granulomas. There appears to be an immunological component to chronic beryllium disease, including the dermal responses. Although available information from epidemiological studies is insufficient to confirm human carcinogenesis, the data strongly suggest beryllium is associated with cancer in humans, and it is categorized as a B1 (probable human carcinogen) by the US Environmental Protection Agency (EPA).
Reproductive Toxicity Little data are available on the reproductive effects of beryllium. Large acute doses have had no effect on reproduction, although continued administration during pregnancy has led to death in utero and quickly after birth. It has also been reported that rats exposed to low levels of beryllium have an increased number of litters.
Genotoxicity Beryllium’s genotoxicity is not entirely clear, owing to weak and/or inconsistent evidence from studies, but there is sufficient evidence to consider it a weak genotoxin. In vitro studies indicate that beryllium induces morphological transformations in mammalian cells, but beryllium is not mutagenic in bacterial systems. There are studies that have exhibited chromosome aberrations in human lymphocytes, as well as increased sister chromatid exchange (SCE).
Carcinogenicity The American Conference of Governmental Industrial Hygienists (ACGIH) classifies beryllium as group TLV-1 (a substance that causes cancer in humans). The DFG maintains the same classification as the ACGIH, although the group is referred to as MAK 1. Also, the IARC classifies it as group 1 (sufficient evidence for carcinogenicity in humans). US EPA classification of beryllium is as groups B1, probable human carcinogen, limited evidence from epidemiological studies, and L, meaning likely to produce cancer in humans. There are several studies suggesting that occupational exposure to beryllium, largely in the form of dust, increases incidence of lung cancer, especially in individuals after recovery from acute beryllium pneumonitis.
Clinical Management Treatment of the acute disease includes bed rest, oxygen therapy, mechanical ventilation when needed, and corticosteroids. Chelation has been used to treat beryllium toxicity; however, no one agent is recommended over another. Aurin tricarboxylic acid has been used to protect primates from beryllium overdose, but human trials have not been conducted.
Beryllium
437
Ecotoxicology
Further Reading
Fish do not accumulate beryllium from water into their bodies to any great extent. A major portion of beryllium in soil does not dissolve in water but remains bound to soil, so it is not very likely to move deeper into the ground and enter groundwater. In the environment, chemical reactions can change the water-soluble beryllium compounds into insoluble forms. In some cases, water-insoluble beryllium compounds can change to soluble forms. Exposure to water-soluble beryllium compounds in the environment, in general, pose a greater threat to human health than water-insoluble forms. No evidence was found to substantiate that biomethylation or any other environmental process results in the volatilization of beryllium into the atmosphere from water or soil. Beryllium is extremely toxic to warm water fish in soft water. The degree of toxicity decreases with increasing water hardness. Bioconcentration of beryllium in fish to high levels is not likely because of the low uptake of beryllium from water by aquatic animals.
Bingham, E., Cohrssen, B., Powell, C.H. (Eds.), 2001. Patty’s Toxicology, fifth ed. John Wiley & Sons, Inc., New York. Gordon, T., Bowser, D., 2003. Beryllium: genotoxicity and carcinogenicity. Mutat. Res. 533, 99–105. Jakubowski, M., Dalezymski, C., 2009. Beryllium. In: Nordberg, G.F., Fowler, B.A., Nordberg, M., Friberg, L.T. (Eds.), Handbook on the Toxicology of Metals, third ed. Elsevier, New York, pp. 416–432. Kreiss, K., 2011. Beryllium: a paradigm for occupational lung disease and its prevention. Occup. Environ. Med. 68 (11), 787–788. Kriebel, D., Brain, J.D., Sprince, N.L., Kazemi, H., 1988. The pulmonary toxicity of beryllium. Am. Rev. Respir. Dis. 137, 464–473. Muller, C., Salehi, F., Mazer, B., Bouchard, M., Adam-Poupart, A., Chevalier, G., Truchon, G., Lambert, J., Zayed, J., 2011 October. Immunotoxicity of 3 chemical forms of beryllium following inhalation exposure. Int. J. Toxicol. 30 (5), 538–545. Nordberg, G.F., Fowler, B.A., Nordberg, M., Friberg, L.T., 2007. Handbook on the Toxicology of Metals, third ed. Associated Press, London. Taylor, T.P., Ding, M., Ehler, D.S., et al., 2003. Beryllium in the environment: a review. J. Environ. Sci. Health A Environ. Sci. Eng. Toxic Hazard. Subst. Control 38, 439–469. Williams, W.J., 1988. Beryllium disease. Postgrad. Med. J. 64, 511–516.
Other Hazards
Relevant Websites
Exposure Standards and Guidelines The ACGIH threshold limit value, 8-h time-weighted average is 0.002 mg m3 for beryllium and beryllium compounds.
Miscellaneous Emeralds are a beryllium compound, beryl, Be3Al2(SiO3)6, which is colored green by the presence of trace quantities of chromium or vanadium.
See also: Metals; Respiratory Tract Toxicology.
http://www.epa.gov/ttn/atw/hlthef/berylliu.html - US Environmental Protection Agency, Air Toxics website: Beryllium Compounds http://minerals.usgs.gov/minerals/pubs/commodity/beryllium/ - US Geological Survey, Minerals Information: Beryllium http://www.cdc.gov/niosh/topics/beryllium/ - Centers for Disease Control, Workplace Safety and Health Topics: Beryllium http://toxnet.nlm.nih.gov/ - Toxnet homepage, search for ‘beryllium’. http://www.epa.gov/iris/toxreviews/0012tr.pdf - US Environmental Protection Agency, Toxicity review of Beryllium.