- Email: [email protected]
Cyanogen bromide
Br
C
N
Cyanogen bromide Toxic Tips
INTRODUCTION
Mechanism of Action
Chemical Description
Cyanogen bromide (BrCN) (CAS Number 50668-3), also known as bromine cyanide or bromocyanogen, is an inorganic cyanide compound that is found as colorless needle or cube crystals. It has a penetrating pungent odor. It is soluble in water, alcohol, and ether. It has a molecular weight of 105.92 and volatilizes at room temperature.1,2 Uses and Typical Exposure Situations
This compound has applications in industry and in the laboratory. It has been used as a reagent in gold extraction, as an intermediate in the synthesis of organic compounds, as a fumigant, and also in cellulose technology and textile treatment.3,4 In the laboratory, it has been used to immobilize proteins by coupling them to reagents such as agarose for affinity chromatography.5 It has also been used in protein structure analysis through its ability to hydrolyze peptide bonds at the C-terminus of methionine residues.6 A solution of cyanogen bromide in water is a reagent in the Niacin production test for identifying strains of Mycobacterium tuberculosis, which is an important procedure for laboratory diagnosis of HIV-opportunistic infections.7 METABOLISM AND PHARMACOKINETICS
Cyanogen bromide can be absorbed by pulmonary, gastrointestinal, and cutaneous routes in the human. Upon entering the blood, cyanogen bromide is quickly hydrolyzed to bromide and cyanide, being distributed to all organs and tissues. Part of the cyanide is excreted unchanged by the lungs, which can give expired air the odor of bitter almonds. A larger portion of the cyanide is converted by sulfurtransferase to the nontoxic thiocyanate ion, which is excreted in the urine. A smaller portion of the cyanide is metabolized by the hepatic enzyme rhodanese, which catalyzes the irreversible reaction of cyanide to produce thiocyanate.8 PATHOPHYSIOLOGY Determinants of Toxicity
The concentration of the airborne dust or vapor, the respiratory rate of the exposed individual, and the time of exposure to the dust or vapor will determine the amount of toxicant reaching the lungs for absorption into the body.
1871-5532/$36.00 doi:10.1016/j.jchas.2009.05.012
When absorbed into the blood, cyanide reacts readily with the trivalent iron of cytochrome oxidase in mitochondria, causing the inhibition of cellular respiration, resulting in cytotoxic hypoxia. This blocks the use of oxygen and as a result venous blood is oxygenated and is almost as bright red as arterial blood. High concentrations of oxyhemoglobin in the venous blood may be confused with carbon monoxide poisoning. Because oxygen cannot be utilized, anaerobic metabolism with the production of lactic acid replaces aerobic metabolism.8
CLINICAL PRESENTATION Effects Following Skin Exposure
Cyanogen bromide is a severe skin irritant and can cause dermal burns after direct contact.4 Effects Following Inhalation
Cyanogen bromide has a pronounced irritant effect on the lungs. High concentrations may cause pulmonary edema and lung hemorrhages. Symptoms of cyanide poisoning can appear within seconds to minutes after breathing vapors—giddiness, hyperpnea, headache, palpitation cyanosis, unconsciousness, asphyxial convulsions, and death. High concentrations of oxyhemoglobin in the venous blood may result in skin color that may be brick red. Cyanosis is not prominent in spite of respiratory symptoms.8 Eye Effects
Cyanogen bromide is irritating to the eyes and has a lacrimatory effect. Direct eye contact may cause severe corneal injury.8 Carcinogenicity
There is no evidence of carcinogenicity in humans or in experimental animals.8 FIRST AID
The primary response to cyanogen bromide exposure is to reduce the exposure, whether by changing into uncontaminated clothes, washing the affected skin thoroughly with soap and water, removing the victim from the contaminated air, or cleaning eyes with an eyewash station for at least 15 min. If systemic cyanide poisoning occurs, an antidote, either hydroxo-
ß Division of Chemical Health and Safety of the American Chemical Society Elsevier Inc. All rights reserved.
29
cobalamin or sodium nitrite/sodium thiosulfate kit, can be administered.8
EXPOSURE CONTROLS Sampling and Analysis
HANDLING AND STORAGE Accidental Release Measures
The first action that should be taken in the case of any accidental release of hazardous chemicals is to evacuate all people who are not wearing adequate protection. After this has been accomplished, it is important to remove all sources of fire, and then collect any cyanogen bromide in a sealable container. Do not touch damaged containers or spilled material unless wearing nitrile rubber gloves, eye protection, protective clothing, and a self-contained breathing apparatus. Do not allow water to make contact with spilled material. The spill area should be thoroughly washed with water and soap after the cyanogen bromide has been collected; then the area should be ventilated. Storage Guidelines
In the laboratory, containers of cyanogen bromide should be kept tightly sealed and stored under nitrogen in a secondary container in a refrigerator.9 If it is to be stored longer than one year at ambient temperature, it should be placed in a 50% weight/volume solution with chloroform. It should always be stored in a cool, dry, well-ventilated location, separate from acids.8 Reactivities and Incompatibilities
Cyanogen bromide corrodes most metals.10 Direct contact with metals may release flammable hydrogen gas. It decomposes to alkali cyanide and alkali bromide when in the presence of aqueous solutions of alkalies.2 It is non-combustible, but when heated may decompose to produce corrosive and/or toxic fumes. It will react with acids to release highly toxic hydrogen cyanide gas. It is incompatible with strong oxidizers, such as nitrates or chlorates. Cyanogen bromide shows evidence of instability, especially in the presence of water or impurities. Impure cyanogen bromide can polymerize during storage, resulting in the danger of explosion.8
30
The National Institute for Occupational Safety and Health (NIOSH) method 7904 for cyanides (aerosol and gas) recommends sampling using a filter plus bubbler (37-mm diameter, 0.8-mm pore size polyvinyl chloride membrane filter plus 15 mL 0.1N KOH in a glass midget bubbler) with an air sampling pump providing a flow rate of 0.5–1 L/min. The cyanide ion (CN ) is analyzed using a cyanide ion electrode.11 Exposure Guidelines
The OSHA permissible exposure limit (PEL) is 5 mg/M3 as an 8-hour time weighted average (TWA) with skin designation for cyanides.12 The American Conference of Governmental Industrial Hygienist (ACGIH) has not assigned a threshold limit value-8 hour time weighted average (TLVTWA) for cyanogen bromide. The DOE temporary emergency exposure limit (TEEL-0) for cyanogen bromide is 20.4 mg/M3. TEEL-0 is the threshold concentration below which most people will experience no adverse health effects.13
PERSONAL PROTECTION
To guard against accidental exposure to cyanogen bromide, an individual working with or around the substance in the absence of local exhaust ventilation should wear protective clothing, including impervious hand protection, as well as a positive pressure self-contained breathing apparatus and chemical safety goggles. Contact lenses should not be worn.
REFERENCES 1. Clayton, G. D., & Clayton, F. (Eds.). Patty’s Industrial Hygiene and Toxicology, Vol. II, Part D Toxicology, 4th ed. John Wiley & Sons, Inc.; New York, NY, 1994, p. 3134–3136. 2. O’Neil, M. J.; Smith, A.; Heckelman, P. E. The Merck Index, 13th ed. Merck & Co; Whitehouse Station, NY, 2001, p. 468.
3. New Jersey Department of Health and Senior Services, Hazardous Substance Fact Sheet: Cyanogen bromide. April 2004. Assessed from http://nj.gov/ health/eoh/rtkweb/documents/fs/ 2302.pdf on May 6, 2009. 4. National Library of Medicine. HazMap: Occupational Exposure to Hazardous Agents. Haz-Map for Cyanogen Bromide, accessed from http:// hazmap.nlm.nih.gov/cgi-bin/hazmap_ search on May 5, 2009. 5. Cuatrecasas, P.; Anfinsen, C. Affinity chromatography. Methods Enzymol. 1977, 22, 345–378. 6. Macmillan, D.; Arham, L. Cyanogen bromide cleavage generates fragments suitable for expressed protein and glycoprotein ligation. J. Am. Chem. Soc. 2004, 126(31), 9530–9531. 7. World Health Organization (WHO), Regional Office for South-East Asia. Blood Safety and Clinical Technology, Guidelines on Standard Operating Procedures for Laboratory Diagnosis of HIV-Opportunistic Infections, accessed from http://www.searo.who.int/en/ Section10/Sect ion17/Section53/ Section367_1134.htm on May 7, 2009. 8. National Library of Medicine. Hazardous Substances Data Bank (HSDB). Fact Sheet for Cyanogen Bromide, accessed from http://toxnet.nlm.nih. gov/cgi-bin/sis/search/f?./temp/ sdBODG:1:FULL on May 6, 2009. 9. National Academy of Sciences (NAS) Commission on Physical Sciences, Mathematics, and Applications (CPSMA). Prudent Practices in the Laboratory; Handling and Disposal of Chemicals, 1995, p. 288. 10. Lewis, R. Sr. Hawley’s Condensed Chemical Dictionary, 15th ed. John Wiley & Sons, Inc.; New York, NY, 2007, p. 355. 11. National Institute for Occupational Safety and Health (NIOSH). Manual of Analytical Methods, 4th ed.; NIOSH, U. S. Public Health Service, Cincinnati, OH, 1994. Accessed Method 7904 for Cyanides, aerosol and gas from http:// www.cdc.gov/niosh/nmam/pdfs/7904 on May 7, 2009. 12. CFR 1910.1000 (USDOL), U.S. National Archives and Records Administration’s Electronic Code of Federal Regulations. Accessed from http:// www.gpoaccess.gov/ecfr on May 7, 2009. 13. Department of Energy (DOE), Protective Action Criteria (PAC) for Chemicals—including AEGLs, ERPGs, & TEELs, 2008. Accessed http://orise.orau.gov/emi/scapa/teels.htm on May 7, 2009.
Journal of Chemical Health & Safety, July/August 2009
C
N
Cyanogen bromide Toxic Tips
INTRODUCTION
Mechanism of Action
Chemical Description
Cyanogen bromide (BrCN) (CAS Number 50668-3), also known as bromine cyanide or bromocyanogen, is an inorganic cyanide compound that is found as colorless needle or cube crystals. It has a penetrating pungent odor. It is soluble in water, alcohol, and ether. It has a molecular weight of 105.92 and volatilizes at room temperature.1,2 Uses and Typical Exposure Situations
This compound has applications in industry and in the laboratory. It has been used as a reagent in gold extraction, as an intermediate in the synthesis of organic compounds, as a fumigant, and also in cellulose technology and textile treatment.3,4 In the laboratory, it has been used to immobilize proteins by coupling them to reagents such as agarose for affinity chromatography.5 It has also been used in protein structure analysis through its ability to hydrolyze peptide bonds at the C-terminus of methionine residues.6 A solution of cyanogen bromide in water is a reagent in the Niacin production test for identifying strains of Mycobacterium tuberculosis, which is an important procedure for laboratory diagnosis of HIV-opportunistic infections.7 METABOLISM AND PHARMACOKINETICS
Cyanogen bromide can be absorbed by pulmonary, gastrointestinal, and cutaneous routes in the human. Upon entering the blood, cyanogen bromide is quickly hydrolyzed to bromide and cyanide, being distributed to all organs and tissues. Part of the cyanide is excreted unchanged by the lungs, which can give expired air the odor of bitter almonds. A larger portion of the cyanide is converted by sulfurtransferase to the nontoxic thiocyanate ion, which is excreted in the urine. A smaller portion of the cyanide is metabolized by the hepatic enzyme rhodanese, which catalyzes the irreversible reaction of cyanide to produce thiocyanate.8 PATHOPHYSIOLOGY Determinants of Toxicity
The concentration of the airborne dust or vapor, the respiratory rate of the exposed individual, and the time of exposure to the dust or vapor will determine the amount of toxicant reaching the lungs for absorption into the body.
1871-5532/$36.00 doi:10.1016/j.jchas.2009.05.012
When absorbed into the blood, cyanide reacts readily with the trivalent iron of cytochrome oxidase in mitochondria, causing the inhibition of cellular respiration, resulting in cytotoxic hypoxia. This blocks the use of oxygen and as a result venous blood is oxygenated and is almost as bright red as arterial blood. High concentrations of oxyhemoglobin in the venous blood may be confused with carbon monoxide poisoning. Because oxygen cannot be utilized, anaerobic metabolism with the production of lactic acid replaces aerobic metabolism.8
CLINICAL PRESENTATION Effects Following Skin Exposure
Cyanogen bromide is a severe skin irritant and can cause dermal burns after direct contact.4 Effects Following Inhalation
Cyanogen bromide has a pronounced irritant effect on the lungs. High concentrations may cause pulmonary edema and lung hemorrhages. Symptoms of cyanide poisoning can appear within seconds to minutes after breathing vapors—giddiness, hyperpnea, headache, palpitation cyanosis, unconsciousness, asphyxial convulsions, and death. High concentrations of oxyhemoglobin in the venous blood may result in skin color that may be brick red. Cyanosis is not prominent in spite of respiratory symptoms.8 Eye Effects
Cyanogen bromide is irritating to the eyes and has a lacrimatory effect. Direct eye contact may cause severe corneal injury.8 Carcinogenicity
There is no evidence of carcinogenicity in humans or in experimental animals.8 FIRST AID
The primary response to cyanogen bromide exposure is to reduce the exposure, whether by changing into uncontaminated clothes, washing the affected skin thoroughly with soap and water, removing the victim from the contaminated air, or cleaning eyes with an eyewash station for at least 15 min. If systemic cyanide poisoning occurs, an antidote, either hydroxo-
ß Division of Chemical Health and Safety of the American Chemical Society Elsevier Inc. All rights reserved.
29
cobalamin or sodium nitrite/sodium thiosulfate kit, can be administered.8
EXPOSURE CONTROLS Sampling and Analysis
HANDLING AND STORAGE Accidental Release Measures
The first action that should be taken in the case of any accidental release of hazardous chemicals is to evacuate all people who are not wearing adequate protection. After this has been accomplished, it is important to remove all sources of fire, and then collect any cyanogen bromide in a sealable container. Do not touch damaged containers or spilled material unless wearing nitrile rubber gloves, eye protection, protective clothing, and a self-contained breathing apparatus. Do not allow water to make contact with spilled material. The spill area should be thoroughly washed with water and soap after the cyanogen bromide has been collected; then the area should be ventilated. Storage Guidelines
In the laboratory, containers of cyanogen bromide should be kept tightly sealed and stored under nitrogen in a secondary container in a refrigerator.9 If it is to be stored longer than one year at ambient temperature, it should be placed in a 50% weight/volume solution with chloroform. It should always be stored in a cool, dry, well-ventilated location, separate from acids.8 Reactivities and Incompatibilities
Cyanogen bromide corrodes most metals.10 Direct contact with metals may release flammable hydrogen gas. It decomposes to alkali cyanide and alkali bromide when in the presence of aqueous solutions of alkalies.2 It is non-combustible, but when heated may decompose to produce corrosive and/or toxic fumes. It will react with acids to release highly toxic hydrogen cyanide gas. It is incompatible with strong oxidizers, such as nitrates or chlorates. Cyanogen bromide shows evidence of instability, especially in the presence of water or impurities. Impure cyanogen bromide can polymerize during storage, resulting in the danger of explosion.8
30
The National Institute for Occupational Safety and Health (NIOSH) method 7904 for cyanides (aerosol and gas) recommends sampling using a filter plus bubbler (37-mm diameter, 0.8-mm pore size polyvinyl chloride membrane filter plus 15 mL 0.1N KOH in a glass midget bubbler) with an air sampling pump providing a flow rate of 0.5–1 L/min. The cyanide ion (CN ) is analyzed using a cyanide ion electrode.11 Exposure Guidelines
The OSHA permissible exposure limit (PEL) is 5 mg/M3 as an 8-hour time weighted average (TWA) with skin designation for cyanides.12 The American Conference of Governmental Industrial Hygienist (ACGIH) has not assigned a threshold limit value-8 hour time weighted average (TLVTWA) for cyanogen bromide. The DOE temporary emergency exposure limit (TEEL-0) for cyanogen bromide is 20.4 mg/M3. TEEL-0 is the threshold concentration below which most people will experience no adverse health effects.13
PERSONAL PROTECTION
To guard against accidental exposure to cyanogen bromide, an individual working with or around the substance in the absence of local exhaust ventilation should wear protective clothing, including impervious hand protection, as well as a positive pressure self-contained breathing apparatus and chemical safety goggles. Contact lenses should not be worn.
REFERENCES 1. Clayton, G. D., & Clayton, F. (Eds.). Patty’s Industrial Hygiene and Toxicology, Vol. II, Part D Toxicology, 4th ed. John Wiley & Sons, Inc.; New York, NY, 1994, p. 3134–3136. 2. O’Neil, M. J.; Smith, A.; Heckelman, P. E. The Merck Index, 13th ed. Merck & Co; Whitehouse Station, NY, 2001, p. 468.
3. New Jersey Department of Health and Senior Services, Hazardous Substance Fact Sheet: Cyanogen bromide. April 2004. Assessed from http://nj.gov/ health/eoh/rtkweb/documents/fs/ 2302.pdf on May 6, 2009. 4. National Library of Medicine. HazMap: Occupational Exposure to Hazardous Agents. Haz-Map for Cyanogen Bromide, accessed from http:// hazmap.nlm.nih.gov/cgi-bin/hazmap_ search on May 5, 2009. 5. Cuatrecasas, P.; Anfinsen, C. Affinity chromatography. Methods Enzymol. 1977, 22, 345–378. 6. Macmillan, D.; Arham, L. Cyanogen bromide cleavage generates fragments suitable for expressed protein and glycoprotein ligation. J. Am. Chem. Soc. 2004, 126(31), 9530–9531. 7. World Health Organization (WHO), Regional Office for South-East Asia. Blood Safety and Clinical Technology, Guidelines on Standard Operating Procedures for Laboratory Diagnosis of HIV-Opportunistic Infections, accessed from http://www.searo.who.int/en/ Section10/Sect ion17/Section53/ Section367_1134.htm on May 7, 2009. 8. National Library of Medicine. Hazardous Substances Data Bank (HSDB). Fact Sheet for Cyanogen Bromide, accessed from http://toxnet.nlm.nih. gov/cgi-bin/sis/search/f?./temp/ sdBODG:1:FULL on May 6, 2009. 9. National Academy of Sciences (NAS) Commission on Physical Sciences, Mathematics, and Applications (CPSMA). Prudent Practices in the Laboratory; Handling and Disposal of Chemicals, 1995, p. 288. 10. Lewis, R. Sr. Hawley’s Condensed Chemical Dictionary, 15th ed. John Wiley & Sons, Inc.; New York, NY, 2007, p. 355. 11. National Institute for Occupational Safety and Health (NIOSH). Manual of Analytical Methods, 4th ed.; NIOSH, U. S. Public Health Service, Cincinnati, OH, 1994. Accessed Method 7904 for Cyanides, aerosol and gas from http:// www.cdc.gov/niosh/nmam/pdfs/7904 on May 7, 2009. 12. CFR 1910.1000 (USDOL), U.S. National Archives and Records Administration’s Electronic Code of Federal Regulations. Accessed from http:// www.gpoaccess.gov/ecfr on May 7, 2009. 13. Department of Energy (DOE), Protective Action Criteria (PAC) for Chemicals—including AEGLs, ERPGs, & TEELs, 2008. Accessed http://orise.orau.gov/emi/scapa/teels.htm on May 7, 2009.
Journal of Chemical Health & Safety, July/August 2009