Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 19 (2015)
Chapter: 1 Cyanide Salts Acute Exposure Guideline Levels
Acute Exposure Guideline Levels
PREFACE
Under the authority of the Federal Advisory Committee Act (FACA) P.L. 92-463 of 1972, the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances (NAC/AEGL Committee) has been established to identify, review, and interpret relevant toxicologic and other scientific data and develop AEGLs for high-priority, acutely toxic chemicals.
AEGLs represent threshold exposure limits for the general public and are applicable to emergency exposure periods ranging from 10 minutes (min) to 8 hours (h). Three levels—AEGL-1, AEGL-2, and AEGL-3—are developed for each of five exposure periods (10 and 30 min and 1, 4, and 8 h) and are distinguished by varying degrees of severity of toxic effects. The three AEGLs are defined as follows:
AEGL-1 is the airborne concentration (expressed as parts per million or milligrams per cubic meter [ppm or mg/m3]) of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic, nonsensory effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure.
____________________
1This document was prepared by the AEGL Development Team composed of Cheryl Bast (Oak Ridge National Laboratory), Heather Carlson-Lynch (SRC, Inc.), Chemical Manager Ralph Gingell (National Advisory Committee [NAC] on Acute Exposure Guideline Levels for Hazardous Substances), and Ernest V. Falke (U.S. Environmental Protection Agency). The NAC reviewed and revised the document and AEGLs as deemed necessary. Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Committee on Acute Exposure Guideline Levels. The NRC committee has concluded that the AEGLs developed in this document are scientifically valid conclusions based on the data reviewed by the NRC and are consistent with the NRC guidelines reports (NRC 1993, 2001).
AEGL-2 is the airborne concentration (expressed as ppm or mg/m3) of a substance above which it is predicted that the general population, including susceptible individuals, could experience irreversible or other serious, long-lasting adverse health effects or an impaired ability to escape.
AEGL-3 is the airborne concentration (expressed as ppm or mg/m3) of a substance above which it is predicted that the general population, including susceptible individuals, could experience life-threatening health effects or death.
Airborne concentrations below the AEGL-1 represent exposure concentrations that could produce mild and progressively increasing but transient and nondisabling odor, taste, and sensory irritation or certain asymptomatic, nonsensory effects. With increasing airborne concentrations above each AEGL, there is a progressive increase in the likelihood of occurrence and the severity of effects described for each corresponding AEGL. Although the AEGL values represent threshold concentrations for the general public, including susceptible subpopulations, such as infants, children, the elderly, persons with asthma, and those with other illnesses, it is recognized that individuals, subject to idiosyncratic responses, could experience the effects described at concentrations below the corresponding AEGL.
SUMMARY
Sodium cyanide, potassium cyanide, and calcium cyanide are simple inorganic cyanide salts with an almond-like odor. They may react with water or moist air to release toxic, corrosive, or flammable gases. Reaction with water may generate heat which will increase the concentration of hydrogen cyanide fumes in the air (HSDB 2005a,b; 2014).
Even though the cyanide salts are solids, inhalation of dusts may result in ionization in the nasal or pulmonary mucosal fluids to yield cyanide. The salts may also react with water in humid air and be inhaled as hydrogen cyanide. In both cases, there will be systemic absorption of cyanide ion, which is the toxic moiety. Cyanide inhibits cellular respiration by blocking electron transfer from cytochrome oxidase to oxygen, causing tissue hypoxia and cell death. Low concentrations or low dose rates of cyanide are tolerated by detoxification by rhodanese to thiocyanate (Kopras 2012).
In the absence of appropriate chemical-specific data on the three cyanide salts, the AEGL-1, AEGL-2, and AEGL-3 values for hydrogen cyanide (NRC 2002) were used to obtain the AEGL values for the salts. Hydrogen cyanide was used as a surrogate for data on the cyanide salts because qualitative (clinical signs) and quantitative (adjusted rat oral LD50 [lethal dose, 50% lethality] values) data suggest that the cyanide moiety is responsible for the acute toxicity of the cyanide salts. Thus, the concentrations of the cyanide salts that would generate hydrogen cyanide concentrations equivalent to that chemical’s AEGL values was calculated. The calculations assumed a temperature of 25°C, a pressure of
760 mm Hg, and complete hydrolysis (one mole of sodium cyanide or potassium cyanide yields one mole of hydrogen cyanide, and one mole of calcium cyanide will yield two moles of hydrogen cyanide).
The calculated AEGL values for the cyanide salts are presented Table 1-1.
1. INTRODUCTION
Sodium cyanide, potassium cyanide, and calcium cyanide are simple inorganic cyanide salts with an almond-like odor. They may react with water or moist air to release toxic, corrosive, or flammable gases. Reaction with water may generate heat which will increase the concentration of hydrogen cyanide fumes in the air (HSDB 2005a,b; 2014).
Even though the salts are solids, inhalation of dusts may result in ionization in the nasal or pulmonary mucosal fluids to yield cyanide. The salts may also react with water in humid air and be inhaled as hydrogen cyanide. In both cases, there will be systemic absorption of cyanide ion, which is the toxic moiety. Cyanide inhibits cellular respiration by blocking electron transfer from cytochrome oxidase to oxygen, causing tissue hypoxia and cell death. Low concentrations or low dose rates of cyanide are tolerated by detoxification by rhodanese to thiocyanate (Kopras 2012).
TABLE 1-1 AEGL Values for Cyanide Saltsa
| Classification | 10 min | 30 min | 1 h | 4 h | 8 h |
| Sodium Cyanide | |||||
| AEGL-1 | 5.0 mg/m3 | 5.0 mg/m3 | 4.0 mg/m3 | 2.6 mg/m3 | 2.0 mg/m3 |
| AEGL-2 | 34 mg/m3 | 20 mg/m3 | 14 mg/m3 | 7.0 mg/m3 | 5.0 mg/m3 |
| AEGL-3 | 54 mg/m3 | 42 mg/m3 | 30 mg/m3 | 17 mg/m3 | 13 mg/m3 |
| Potassium Cyanide | |||||
| AEGL-1 | 6.6 mg/m3 | 6.6 mg/m3 | 5.3 mg/m3 | 3.5 mg/m3 | 2.7 mg/m3 |
| AEGL-2 | 45 mg/m3 | 27 mg/m3 | 19 mg/m3 | 9.3 mg/m3 | 6.6 mg/m3 |
| AEGL-3 | 72 mg/m3 | 56 mg/m3 | 40 mg/m3 | 23 mg/m3 | 18 mg/m3 |
| Calcium Cyanideb | |||||
| AEGL-1 | 4.7 mg/m3 | 4.7 mg/m3 | 3.8 mg/m3 | 2.4 mg/m3 | 1.9 mg/m3 |
| AEGL-2 | 32 mg/m3 | 19 mg/m3 | 13 mg/m3 | 6.6 mg/m3 | 4.7 mg/m3 |
| AEGL-3 | 51 mg/m3 | 39 mg/m3 | 28 mg/m3 | 16 mg/m3 | 12 mg/m3 |
aAirborne concentrations of these salts will produce the equivalent AEGL values for hydrogen cyanide.
bAlthough the adjusted rat oral LD50 value for calcium cyanide is much greater than would be expected on a molar basis for cyanide (suggesting that it is a less toxic compound), the production of two moles of hydrogen cyanide was assumed per mole of calcium cyanide. That assumption will yield protective AEGL values.
The rate of cyanide generation depends on ambient temperature, humidity, pH, and the particular cyanide salt; sodium and potassium cyanide behave differently than calcium cyanide. In moist air and at normal temperature, sodium and potassium cyanide slowly decompose and generate hydrogen cyanide (Gail et al. 2011). In the presence of strong acids, complete decomposition and release of hydrogen cyanide occurs (Gail et al. 2011). In dry air, both sodium and potassium cyanide are stable even at high temperatures (Gail et al. 2011).
The alkaline earth cyanides (such as calcium cyanide) are less stable than the alkali metal cyanides (sodium or potassium cyanides) (Gail et al. 2011). Alkaline earth metal cyanides decompose at high temperature, generating hydrogen cyanide. In addition, alkaline earth metal cyanides readily hydrolyze in moist air to release hydrogen cyanide (Pesce 2010; Gail et al. 2011). The amount of hydrogen cyanide released from commercially-produced calcium cyanide (for fumigation purposes) is about 50% of the weight of the cyanide in granular formulation (FAO 1965; Bond 1984).
Hydrolysis constants for sodium and potassium cyanide are similar (2.51 × 10-5 and 2.54 × 10-5, respectively, at 25°C) (Pesce 2010); data on the hydrolysis of calcium cyanide were not found. Hydrolysis reactions for the three cyanide salts are shown below (Pesce 2010). One mole of sodium cyanide or potassium cyanide may react with water or moisture to produce a maximum of one mole of hydrogen cyanide by the following reactions:
NaCN + H2O → HCN + NaOH
KCN+ H2O → HCN + KOH
One mole of calcium cyanide may react with water or moisture to produce a maximum of two moles of hydrogen cyanide by the following reaction:
Ca(CN)2 + 2H2O → 2HCN + Ca(OH)2
Sodium cyanide is a white crystalline solid, and may be prepared by heating sodium amide with carbon or by melting sodium chloride and calcium cyan-amide together in an electric furnace. It is used for extracting gold and silver from ores, heat treating of metals, electroplating, various organic reactions, and the manufacturing of adiponitrile (Kopras 2012). US production of sodium cyanide was reported as “at least” 1.14 × 1011 grams in 1977, and US imports were reported as 2.77 × 107 pounds in 1986 (HSDB 2005a).
Potassium cyanide, a white crystalline solid, is prepared by reaction of an aqueous solution of potassium hydroxide with hydrogen cyanide. It is used for fine silver plating, dyes and specialty products, and fumigation of fruit trees, ships, railway cars, and warehouses. US production information was not available; however, US imports were reported as 1,468,423 pounds in 1987 (HSDB 2005b).
Calcium cyanide is a white powder, and is prepared from lime, calcium oxide, coke, and nitrogen in an electric furnace. The commercial product is dark
gray because of the presence of carbon. It is used in the extraction of precious metal ores, adsorption of gold complexes on carbon, as a fumigant, and as a rodenticide (Kopras 2012). US production information on calcium cyanide was not available; however, US imports were reported as 468,246 pounds in 1986 (HSDB 2014).
The chemical and physical properties of the three cyanide salts are presented in Tables 1-2, 1-3, and 1-4.
TABLE 1-2 Chemical and Physical Properties of Sodium Cyanide
| Parameter | Value | References |
| Synonyms | Cyanogran; cyanide of sodium; cymag; hydrocyanic acid sodium salt; cyanobrik; white cyanide | Kopras 2012 |
| CAS registry no. | 143-33-9 | HSDB 2005a |
| Chemical formula | NaCN | HSDB 2005a |
| Molecular weight | 49.0 | HSDB 2005a |
| Physical state | White crystalline solid | HSDB 2005a |
| Melting point | 563°C | HSDB 2005a |
| Boiling point | 1,496°C | HSDB 2005a |
| Density/specific gravity | 1.595 g/cm3 at 20°C | HSDB 2005a |
| Solubility in water | 48 g/100 mL water at 10°C; forms HCN | HSDB 2005a |
| Vapor pressure | 1 mm Hg at 817°C | HSDB 2005a |
| Hydrolysis constant | 2.51 × 10-5 per second at 25°C; yields calculated | Pesce 2010 |
| half-life of 7.7 h | ||
| Conversion factors | 1 ppm = 2.0 mg/m3 | |
| 1 mg/m3 = 0.50 ppm | ||
TABLE 1-3 Chemical and Physical Properties of Potassium Cyanide
| Parameter | Value | References |
| Synonyms | Hydrocyanic acid potassium salt | Kopras 2012 |
| CAS registry no. | 151-50-8 | HSDB 2005b |
| Chemical formula | KCN | HSDB 2005b |
| Molecular weight | 65.11 | HSDB 2005b |
| Physical state | White crystalline solid | HSDB 2005b |
| Melting point | 634°C | HSDB 2005b |
| Density/specific gravity | 1.55 at 20°C | HSDB 2005b |
| Solubility in water | 100 g/100 mL water at >176°F; forms HCN | HSDB 2005b |
| Hydrolysis constant | 2.54 × 10-5 per sec at 25°C; calculated half-life of 7.6 h | Pesce 2010 |
| Conversion factors | 1 ppm = 2.7 mg/m3 1 mg/m3 = 0.38 ppm |
|
TABLE 1-4 Chemical and Physical Properties of Calcium Cyanide
| Parameter | Value | References |
| Synonyms | Calcyanide; cyanogas; black cyanide, aero; calcium cyanide, tech grade | Kopras 2012 |
| CAS registry no. | 592-01-8 | HSDB 2014 |
| Chemical formula | Ca(CN)2 | HSDB 2014 |
| Molecular weight | 92.12 | HSDB 2014 |
| Physical state | White powder, solid | HSDB 2014 |
| Melting point | 640°C (estimated by extrapolation because of decomposition) | HSDB 2014 |
| Density/specific gravity | 1.853 at 20°C | HSDB 2014 |
| Solubility in water | Soluble in water, gradual liberation of HCN | HSDB 2014 |
| Conversion factors | 1 ppm = 3.8 mg/m3 1 mg/m3 = 0.27 ppm |
|
2. HUMAN TOXICITY DATA
No human toxicity data on sodium, potassium, or calcium cyanide were found. There are numerous reports of occupational exposure to hydrogen cyanide (see NRC 2002).
3. ANIMAL TOXICITY DATA
No animal toxicity data on sodium, potassium, or calcium cyanide were found. However, the toxicity data base for hydrogen cyanide is robust. Lethality data are available from studies of dogs, rats, mice, and rabbits, and nonlethal toxicity data are available from studies of nonhuman primates, rats, and mice (see NRC 2002).
4. SPECIAL CONSIDERATIONS
4.1. Metabolism and Disposition
Solid cyanide salts deposited on moist respiratory-tract surfaces may hydrolyze and release absorbable cyanide. Another scenario would involve atmospheric hydrolysis of metal cyanides to hydrogen cyanide vapor. Metabolism and disposition information on hydrogen cyanide is summarized in NRC (2002).
Dermal absorption of cyanide salts depends on the form of the salt and the condition of the skin. Dermal exposure to cyanide salts in solution, or exposure of moist or abraded skin to dry cyanide salts, can result in significant absorption of cyanide ion or hydrogen cyanide (Ballantyne 1987). The permeability of cyanide ion across human skin in vitro was estimated to be 3.5 × 10-4 cm/h, and the
permeability of hydrogen cyanide was 100 × 10-4 cm/h (Dugard 1987). In addition, skin exposure to very high air concentrations of hydrogen cyanide has resulted in human poisoning (Potter 1950).
4.2. Mechanism of Toxicity
Hydrogen cyanide is a systemic poison that acts on the central nervous system. Hydrogen cyanide interrupts cellular respiration by blocking electron transfer from cytochrome oxidase to oxygen. Tissue concentrations of oxygen rise, resulting in increased tissue oxygen tension and decreased unloading for oxyhemoglobin. As a consequence, oxidative metabolism may slow to a point where it cannot meet metabolic demands. This is particularly critical in the brainstem nuclei where lack of an energy source results in central respiratory arrest and death. Cyanide can inhibit many other enzymes, particularly those that contain iron or copper, but cytochrome oxidase appears to be the most sensitive enzyme. Cyanide also stimulates the chemoreceptors of the carotid and aortic bodies to produce a brief period of hyperpnea. Cardiac irregularities may occur, but death is due to respiratory arrest (Smith 1996; Kopras 2012). Brain lesions in animals have been associated with exposure to hydrogen cyanide at high concentrations (ATSDR 2006).
4.3. Structure-Activity Relationships
As noted earlier, no acute inhalation toxicity data on the cyanide salts were available. However, acute oral toxicity data suggest both qualitatively (clinical signs) and quantitatively (rat LD50 values) that the cyanide moiety is responsible for the acute toxicity of the cyanide salts. Cyanide-induced clinical effects are indistinguishable in humans and animals after inhalation or dermal exposure to hydrogen cyanide vapor or after oral exposure to sodium or potassium cyanide. Clinical signs include headaches, dizziness, nausea, inability to concentrate, thoracic oppression, palpitation, numbness, weakness, rapid pulse, face flushing, unconsciousness, and death (Kopras 2012).
Rat oral LD50 values support the contention that cyanide is the toxic moiety. The LD50 values for the salts and the LD50 values adjusted as equivalent doses of cyanide are presented in Table 1-5. The adjusted values for hydrogen, sodium, and potassium cyanide are comparable whereas the adjusted value for calcium cyanide is much greater (suggesting a less toxic compound) than would be expected on a molar basis for cyanide. The difference may be due to a slower hydrolysis rate, allowing for more efficient detoxification, relative to the other cyanide salts. (Although hydrolysis rates were not found, water solubility/reactivity is described as “forms hydrogen cyanide” for sodium and potassium cyanides [HSDB 2005a,b], and “gradually liberates hydrogen cyanide” for calcium cyanide [HSDB 2014]).
TABLE 1-5 Lethality in Rats Exposed Orally to Hydrogen Cyanide and Cyanide Salts
| Compound | LD50, mg/kg (sex) | Adjusted LD50, mg/kg CN- | Reference |
| HCN | 4.2 (F) | 4.1 | Ballantyne 1987 |
| NaCN | 5.7 (F) | 3.0 | Ballantyne 1987 |
| 15 (M) | 8.0 | Smyth et al. 1969 | |
| KCN | 7.5 (F) | 3.0 | Ballantyne 1987 |
| 10 (M) | 4.0 | Hayes 1967 | |
| 6 (M) | 2.4 | Lorke 1983 | |
| Ca(CN)2 | 39 (M) | 22 | Smyth et al. 1969 |
4.4. Other Relevant Information
4.4.1. Concurrent Exposure Issues
Because hydrogen cyanide is the toxic moiety of all three salts, and may also be generated by other compounds, coexposure to multiple cyanide salts or other sources of cyanide will result in greater cumulative exposure to cyanide. Exposures should be expressed as cyanide ion and compared with the AEGLs expressed in the same manner to ensure that cumulative exposure is evaluated.
5. DATA ANALYSIS FOR AEGL-1
5.1. Human Data Relevant to AEGL-1
No human data relevant to developing AEGL-1 values for the cyanide salts were found.
5.2. Animal Data Relevant to AEGL-1
No animal data relevant to developing AEGL-1 values for the cyanide salts were found.
5.3. Derivation of AEGL-1 Values
In the absence of appropriate chemical-specific data for the cyanide salts, the AEGL-1 values for hydrogen cyanide (NRC 2002) were used to obtain AEGL-1 values for them. The use of hydrogen cyanide as a surrogate for the cyanide salts is deemed appropriate because qualitative (clinical signs) and quantitative (adjusted rat oral LD50 values) data suggest that the cyanide moiety is responsible for the acute toxicity of the cyanide salts. In addition, because hydrolysis of cyanide salts in the air or moist respiratory tract may be incomplete (whereas hydrolysis is likely complete after oral exposure due to the low pH of the stomach), the use of hydrogen cyanide as a surrogate for derivation of AEGL values is expected to be conservative.
The hydrogen cyanide AEGL-1 values were used as target values for calculating the concentrations of cyanide salt needed to generate the hydrogen cyanide AEGL values. The calculations assumed a temperature of 25°C, a pressure of 760 mm Hg, and complete hydrolysis. The AEGL-1 values for the cyanide salts are presented in Table 1-6, the calculations are presented in Appendix A, and derivation summary tables are provided in Appendix C. For comparison, the calculations and AEGL derivation summary tables for hydrogen cyanide are presented in Appendix B and Appendix D, respectively.
6. DATA ANALYSIS FOR AEGL-2
6.1. Human Data Relevant to AEGL-2
No human data relevant to developing AEGL-2 values for the cyanide salts were found.
6.2. Animal Data Relevant to AEGL-2
No animal data relevant to developing AEGL-2 values for the cyanide salts were found.
6.3. Derivation of AEGL-2 Values
In the absence of appropriate chemical-specific data for the cyanide salts, the AEGL-2 values for hydrogen cyanide (NRC 2002) were used to obtain AEGL-2 values for the title cyanide salts. The use of hydrogen cyanide as a surrogate for the cyanide salts is deemed appropriate because qualitative (clinical signs) and quantitative (adjusted rat oral LD50 values) data suggest that the cyanide moiety is responsible for acute toxicity of the cyanide salts. In addition, because hydrolysis of cyanide salts in the air or moist respiratory tract may be incomplete (whereas hydrolysis is likely complete after oral exposure due to the low pH of the stomach), the use of hydrogen cyanide as a surrogate for derivation of AEGL values is expected to be conservative.
The hydrogen cyanide AEGL-2 values were used as target values for calculating the concentrations of cyanide salt needed to generate the hydrogen cyanide AEGL values. The calculations assumed a temperature of 25°C, a pressure of 760 mm Hg, and complete hydrolysis. The AEGL-2 values for the cyanide salts are presented in Table 1-7, the calculations are presented in Appendix A, and derivation summary tables for the cyanide salts are provided in Appendix C. For comparison, the calculations and AEGL derivation summary tables for hydrogen cyanide are presented in Appendix B and Appendix D, respectively.
TABLE 1-6 AEGL-1 Values for Cyanide Saltsa
| Compound | 10 min | 30 min | 1 h | 4 h | 8 h |
| Sodium cyanide | 5.0 mg/m3 | 5.0 mg/m3 | 4.0 mg/m3 | 2.6 mg/m3 | 2.0 mg/m3 |
| Potassium cyanide | 6.6 mg/m3 | 6.6 mg/m3 | 5.3 mg/m3 | 3.5 mg/m3 | 2.7 mg/m3 |
| Calcium cyanideb | 4.7 mg/m3 | 4.7 mg/m3 | 3.8 mg/m3 | 2.4 mg/m3 | 1.9 mg/m3 |
aAirborne concentrations of these salts will produce the equivalent AEGL values for hydrogen cyanide.
bAlthough the adjusted rat oral LD50 value for calcium cyanide is much greater than would be expected on a molar basis for cyanide (suggesting that it is a less toxic compound), the production of two moles of hydrogen cyanide was assumed per mole of calcium cyanide. That assumption will yield protective AEGL values.
TABLE 1-7 AEGL-2 Values for Cyanide Saltsa
| Compound | 10 min | 30 min | 1 h | 4 h | 8 h |
| Sodium cyanide | 34 mg/m3 | 20 mg/m3 | 14 mg/m3 | 7.0 mg/m3 | 5.0 mg/m3 |
| Potassium cyanide | 45 mg/m3 | 27 mg/m3 | 19 mg/m3 | 9.3 mg/m3 | 6.6 mg/m3 |
| Calcium cyanideb | 32 mg/m3 | 19 mg/m3 | 13 mg/m3 | 6.6 mg/m3 | 4.7 mg/m3 |
aAirborne concentrations of these salts will produce the equivalent AEGL values for hydrogen cyanide.
bAlthough the adjusted rat oral LD50 value for calcium cyanide is much greater than would be expected on a molar basis for cyanide (suggesting that it is a less toxic compound), the production of two moles of hydrogen cyanide was assumed per mole of calcium cyanide. That assumption will yield protective AEGL values.
7. DATA ANALYSIS FOR AEGL-3
7.1. Human Data Relevant to AEGL-3
No human data relevant to developing AEGL-3 values for the cyanide salts were found.
7.2. Animal Data Relevant to AEGL-3
No animal data relevant to developing AEGL-3 values for the cyanide salts were found.
7.3. Derivation of AEGL-3 Values
In the absence of appropriate chemical-specific data for the title cyanides, the AEGL-3 values for hydrogen cyanide (NRC 2002) were used to obtain AEGL-3 values for the title cyanide salts. The use of hydrogen cyanide as a surrogate for the cyanide salts is deemed appropriate because qualitative (clinical signs) and quantitative (adjusted rat oral LD50 values) data suggest that the cyanide moiety is responsible for acute toxicity of the cyanide salts. In addition,
because hydrolysis of cyanide salts in the air or moist respiratory tract may be incomplete (whereas hydrolysis is likely complete after oral exposure due to the low pH of the stomach), the use of hydrogen cyanide as a surrogate for derivation of AEGL values is expected to be conservative.
The hydrogen cyanide AEGL-3 values were used as target values for calculating the concentrations of cyanide salt needed to generate the hydrogen cyanide AEGL values. The calculations assumed a temperature of 25°C, a pressure of 760 mm Hg, and complete hydrolysis. The AEGL-3 values for the cyanide salts are presented in Table 1-8, the calculations are presented in Appendix A, and derivation summary tables for cyanide salts are provided in Appendix C. For comparison, the calculations and AEGL derivation summary tables for hydrogen cyanide are presented in Appendix B and Appendix D, respectively.
8. SUMMARY OF AEGLS
8.1. AEGL Values and Toxicity End Points
The AEGL values for the cyanide salts are presented in Table 1-9. They are based on molar adjustments of the AEGL values for hydrogen cyanide (NRC 2002).
8.2. Comparison with Other Standards and Guidelines
Exposure standards and guidelines for the cyanide salts are presented in Table 1-10, and are expressed in terms of cyanide ion. The 10-min AEGL-1 value for the cyanide salts (2.7 mg/m3) is in reasonably good agreement with the short-term exposure limit of 5 mg/m3 established by the American Conference of Governmental Industrial Hygienists (ACGIH 2001, 2013) and the National Institute for Occupational Safety and Health (NIOSH 2011). Likewise, the 30-min AEGL-3 value of 22 mg/m3 for the cyanide salts is similar to the NIOSH (1994) immediately dangerous to life or health value of 25 mg/m3.
TABLE 1-8 AEGL-3 Values for Cyanide Saltsa
| Compound | 10 min | 30 min | 1 h | 4 h | 8 h |
| Sodium cyanide | 54 mg/m3 | 42 mg/m3 | 30 mg/m3 | 17 mg/m3 | 13 mg/m3 |
| Potassium cyanide | 72 mg/m3 | 56 mg/m3 | 40 mg/m3 | 23 mg/m3 | 18 mg/m3 |
| Calcium cyanideb | 51 mg/m3 | 39 mg/m3 | 28 mg/m3 | 16 mg/m3 | 12 mg/m3 |
aAirborne concentrations of these salts will produce the equivalent AEGL values for hydrogen cyanide.
bAlthough the adjusted rat oral LD50 value for calcium cyanide is much greater than would be expected on a molar basis for cyanide (suggesting that it is a less toxic compound), the production of two moles of hydrogen cyanide was assumed per mole of calcium cyanide. That assumption will yield protective AEGL values.
TABLE 1-9 AEGL Values for Cyanide Saltsa
| Classification | 10 min | 30 min | 1 h | 4 h | 8 h |
| Sodium Cyanide | |||||
| AEGL-1 | 5.0 mg/m3 | 5.0 mg/m3 | 4.0 mg/m3 | 2.6 mg/m3 | 2.0 mg/m3 |
| AEGL-2 | 34 mg/m3 | 20 mg/m3 | 14 mg/m3 | 7.0 mg/m3 | 5.0 mg/m3 |
| AEGL-3 | 54 mg/m3 | 42 mg/m3 | 30 mg/m3 | 17 mg/m3 | 13 mg/m3 |
| Potassium Cyanide | |||||
| AEGL-1 | 6.6 mg/m3 | 6.6 mg/m3 | 5.3 mg/m3 | 3.5 mg/m3 | 2.7 mg/m3 |
| AEGL-2 | 45 mg/m3 | 27 mg/m3 | 19 mg/m3 | 9.3 mg/m3 | 6.6 mg/m3 |
| AEGL-3 | 72 mg/m3 | 56 mg/m3 | 40 mg/m3 | 23 mg/m3 | 18 mg/m3 |
| Calcium Cyanideb | |||||
| AEGL-1 | 4.7 mg/m3 | 4.7 mg/m3 | 3.8 mg/m3 | 2.4 mg/m3 | 1.9 mg/m3 |
| AEGL-2 | 32 mg/m3 | 19 mg/m3 | 13 mg/m3 | 6.6 mg/m3 | 4.7 mg/m3 |
| AEGL-3 | 51 mg/m3 | 39 mg/m3 | 28 mg/m3 | 16 mg/m3 | 12 mg/m3 |
aAirborne concentrations of these salts will produce the equivalent AEGL values for hydrogen cyanide.
bAlthough the adjusted rat oral LD50 value for calcium cyanide is much greater than would be expected on a molar basis for cyanide (suggesting that it is a less toxic compound), the production of two moles of hydrogen cyanide was assumed per mole of calcium cyanide. That assumption will yield protective AEGL values.
TABLE 1-10 Standards and Guidelines for Cyanide Salts (Expressed as CN-)
| Exposure Duration | |||||
| Guideline | 10 min | 30 min | 1 h | 4 h | 8 h |
| AEGL-1 | 2.7 mg/m3 | 2.7 mg/m3 | 2.1 mg/m3 | 1.3 mg/m3 | 1.1 mg/m3 |
| AEGL-2 | 18 mg/m3 | 11 mg/m3 | 7.5 mg/m3 | 3.8 mg/m3 | 2.7 mg/m3 |
| AEGL-3 | 29 mg/m3 | 22 mg/m3 | 16 mg/m3 | 9.1 mg/m3 | 7.0 mg/m3 |
| IDLH (NIOSH)a | – | 25 mg/m3 | – | – | – |
| PEL-TWA (OSHA)b | – | – | – | – | 11 mg/m3 |
| TLV-STEL (ACGIH)c | 5.0 mg/m3 | – | – | – | – |
| REL-STEL (NIOSH)d | 5.0 mg/m3 | – | – | – | – |
| MAK (Germany)e | – | – | – | – | 2.0 mg/m3 |
| MAC-Peak Category | 10 mg/m3 | – | – | – | 1.0 mg/m3 |
| (The Netherlands)f | [15 min] | ||||
| CLV (Sweden)g | – | – | – | – | 5.0 mg/m3 |
aIDLH (immediately dangerous to life or health, National Institute for Occupational Safety and Health) (NIOSH 1994) represents the maximum concentration from which one could escape within 30 min without any escape-impairing symptoms, or any irreversible health effects.
bPEL-TWA (permissible exposure limit – time-weighted average, Occupational Safety and Health Administration) (OSHA 1978) is the time-weighted average concentrations for a 10-h workday and a 40-h workweek, to which nearly all workers may be repeatedly exposed, day after day, without adverse effect.
cTLV-STEL (threshold limit value – short-term exposure limit, American Conference of Governmental Industrial Hygienists) (ACGIH 2001, 2013) is defined as a 15-min time-weighted average exposure which should not be exceeded at any time during the workday even if the 8-h time-weighted average is within the threshold-limit value–time-weighted average. Exposures above the threshold-limit value–time-weighted average up to the STEL should not be longer than 15 min and should not occur more than four times per day. There should be at least 60 min between successive exposures in that range. Value is for hydrogen cyanide and sodium, potassium, and calcium cyanides (as cyanide).
dREL-STEL (recommended exposure limits – short-term exposure limit, National Institute for Occupational Safety and Health) (NIOSH 2011) is defined analogous to the ACGIH TLV-STEL.
eMAK (maximale arbeitsplatzkonzentration [maximum workplace concentration], Deutsche Forschungsgemeinschaft [German Research Association]) (DFG 2007) is the time-weighted average concentrations for a normal 8-h workday and a 40-h workweek, to which nearly all workers may be repeatedly exposed, day after day, without adverse effect.
fMAC (maximaal aanvaaarde concentratie [maximal accepted concentration - peak category], Dutch Expert Committee for Occupational Standards, The Hague, The Netherlands (MSZW 2007) is defined analogous to the ACGIH-ceiling.
gCLV (ceiling limit value, Swedish Work Environment Authority) (SWEA 2005) is the maximum acceptable average concentration limit value (time-weighted average) for a workday. Value is for cyanides and hydrogen cyanide (as CN) total dust.
8.3. Data Adequacy and Research Needs
There are no human or animal inhalation data for sodium, potassium, or calcium cyanide. However, data suggest that the cyanide moiety is responsible for the acute toxicity of these compounds, and the hydrogen cyanide data set is fairly robust.
9. REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). 2001. Documentation of the Threshold Limit Values and Biological Exposure Indices: Hydrogen Cyanide and Cyanide Salts, as CN. American Conference of Governmental Industrial Hygienists, Inc., Cincinnati, OH.
ACGIH (American Conference of Governmental Industrial Hygienists). 2013. 2013 Threshold Limit Values and Biological Exposure Indices Based on the Documentation of the TLVs for Chemical Substances and Physical Agents and BEIs. American Conference of Governmental Industrial Hygienists, Inc., Cincinnati, OH.
ATSDR (Agency for Toxic Substances and Disease Registry). 2006. Toxicological Profile for Cyanide. U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry, Atlanta, GA [online]. Available: http://www.atsdr.cdc.gov/toxprofiles/tp8.pdf [accessed Nov. 19, 2014].
Ballantyne, B. 1987. Toxicology of cyanides. Pp. 41-126 in Clinical and Experimental Toxicology of Cyanides, B. Ballantyne, and T.C. Marrs, eds. Bristol: Wright.
Bond, E.J. 1984. Manual of Fumigation for Insect Control. FAO Plant Production and Protection Papers No. 54. Rome: Food and Agriculture Organization of the United
Nations [online]. Available: http://www.fao.org/docrep/X5042E/X5042E00.htm [accessed Nov. 19, 2014].
DFG (Deutsche Forschungsgemeinschaft). 2007. List of MAK and BAT Values 2007: Maximum Concentrations and Biological Tolerance Values at the Workplace. Report No. 43. Weinheim, Germany: Wiley-VCH.
Dugard, P.H. 1987. The absorption of cyanide through human skin in vitro from solutions of sodium cyanide and gaseous HCN. Pp. 127-137 in Clinical and Experimental Toxicology of Cyanides, B. Ballantyne, and T.C. Marrs, eds. Bristol: Wright.
El Ghawabi, S.H., M.A. Gaafar, A.A. El-Saharti, S.H. Ahmed, K.K. Malash, and R. Fares. 1975. Chronic cyanide exposure: A clinical, radioisotope, and laboratory study. Br. J. Ind. Med. 32(3):215-219.
FAO (Food and Agriculture Organization of the United Nations). 1965. Evaluation of the Hazards to Consumers Resulting from the Use of Fumigants in the Protection of Food. Joint Meeting of the FAO Committee on Pesticides in Agriculture and the WHO Expert Committee on Pesticide Residues, March 15-22, 1965. FAO Meeting Report No. PL/1965/10/2; WHO/Food Add/28.65. Rome: FAO.
Gail, E., S. Gos, R. Kulzer, J. Lorosch, A. Rubo, M. Sauer, R. Kellens, J. Reddy, N. Steier, and W. Hasenpusch. 2011. Cyano compounds, inorganic. In Ullmann’s Encyclopedia of Industrial Chemistry. Wiley Online Library.
Grabois, B. 1954. Exposure to hydrogen cyanide in processing of apricot kernels. Monthly Review NY Department of Labor 33(September):33-36.
Hardy, H.L., W.M. Jeffries, M.M. Wasserman, and W.R. Waddell. 1950. Thiocyanate effect following industrial cyanide exposure - report of two cases. New Engl. J. Med. 242(25):968-972.
Haskell Laboratory. 1981. Inhalation Toxicity of Common Combustion Gases. Haskell Laboratory Report No. 238-81. E.I. du Pont de Nemours and Company, Haskell Laboratory for Toxicology and Industrial Medicine, Newark, DE.
Hayes, W.J. 1967. The 90-day LD50 and chronicity factors as a measure of toxicity. Toxicol. Appl. Pharmacol. 11:327-335.
HSDB (Hazardous Substances Data Bank). 2005a. Sodium Cyanide (CASRN 143-33-9). TOXNET Toxicology Data Network, U.S. National Library of Medicine, Bethesda, MD [online]. Available: http://toxnet.nlm.nih.gov/cgi-bin/sis [accessed Nov. 19, 2014].
HSDB (Hazardous Substances Data Bank). 2005b. Potassium Cyanide (CASRN 151-50-8). TOXNET Toxicology Data Network, U.S. National Library of Medicine, Bethesda, MD [online]. Available: http://toxnet.nlm.nih.gov/cgi-bin/sis [accessed Nov. 19, 2014].
HSDB (Hazardous Substances Data Bank). 2014. Calcium Cyanide (CASRN 592-01-8). TOXNET Toxicology Data Network, U.S. National Library of Medicine, Bethesda, MD [online]. Available: http://toxnet.nlm.nih.gov/cgi-bin/sis [accessed Nov. 19, 2014].
Kopras, E.J. 2012. Cyanides and nitriles. In Patty’s Toxicology. Wiley Online Library.
Leeser, J.E., J.A. Tomenson, and D.D. Bryson. 1990. A Cross-Sectional Study of the Health of Cyanide Salt Production Workers. Report No. OHS/R/2, ICI Central Toxicology Laboratory, Macclesfield, UK. January 12, 1990.
Lorke, D. 1983. A new approach to practical acute toxicity testing. Arch. Toxicol. 54(4):275-287.
Maehly, A.C., and A. Swensson. 1970. Cyanide and thiocyanate levels in blood and urine of workers with low-grade exposure to cyanide. Int. Arch. Arbeitsmed. 27(3):195-209.
MSZW (Ministerie van Sociale Zaken en Werkgelegenheid). 2007. OEL Database: Hydrogen Cyanide. The Social and Economic Council of the Netherlands, The Hague [online]. Available: http://www.ser.nl/en/grenswaarden/hydrogen%20cyanide.aspx [accessed Nov. 19, 2014].
NIOSH (National Institute for Occupational Safety and Health). 1976. Pp. 37-114 in Criteria for a Recommended Standard. Occupational Exposure to Hydrogen Cyanide and Cyanide Salts (NaCN, KCN, and Ca(CN2)). DHEW (NIOSH) Pub. No. 77-108. PB 266 230. U.S. Department of Health, Education, and Welfare, National Institute for Occupational Safety and Health, Washington, DC.
NIOSH (National Institute for Occupational Safety and Health). 1994. Documentation for Immediately Dangerous to Life or Health Concentrations (IDLHs): Cyanides (as CN) [online]. Available: http://www.cdc.gov/niosh/idlh/cyanides.html [accessed Nov. 19, 2014].
NIOSH (National Institute for Occupational Safety and Health). 2011. NIOSH Pocket Guide to Chemical Hazards: Hydrogen Cyanide [online]. Available: http://www.cdc.gov/niosh/npg/npgd0333.html [accessed Nov. 19, 2014].
NRC (National Research Council). 1993. Guidelines for Developing Community Emergency Exposure Levels for Hazardous Substances. Washington, DC: National Academy Press.
NRC (National Research Council). 2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals. Washington, DC: National Academy Press.
NRC (National Research Council). 2002. Hydrogen Cyanide. Pp. 211-276 in Acute Exposure Guideline Levels for Selected Airborne Chemicals, Vol. 2. Washington, DC: The National Academies Press.
OSHA (Occupational Health and Safety Administration). 1978. Occupational Health Guideline for Hydrogen Cyanide. U.S. Department of Health and Human Services and U.S. Department of Labor. September 1978 [online]. Available; http://www.cdc.gov/niosh/docs/81-123/pdfs/0333.pdf [accessed Nov. 20, 2014].
Pesce, L.D. 2010. Cyanides. In Kirk-Othmer Encyclopedia of Chemical Technology. Wiley Online Library.
Potter, L. 1950. The successful treatment of two recent cases of cyanide poisoning. Br. J. Ind. Med. 7(3):125-130.
Purser, D.A. 1984. A bioassay model for testing the incapacitating effects of exposure to combustion product atmospheres using cynomolgus monkeys. J. Fire Sci. 2:20-36.
Purser, D.A., P. Grimshaw, and K.R. Berrill. 1984. Intoxication by cyanide in fires: A study in monkeys using polyacrylonitrile. Arch. Environ. Health 39(6):394-400.
Smith, R.P. 1996. Toxic responses of the blood. Pp. 335-354 in Casarett and Doull’s Toxicology: The Basic Science of Poisons, 5th Ed., C.D. Klaassen, ed. New York: McGraw-Hill.
Smyth, H.F., C.P. Carpenter, C.S. Weil, U.C. Pozzani, J.A. Striegel, and J.S. Nycum. 1969. Range-finding toxicity data: List VII. Am. Ind. Hyg. Assoc. J. 30(5):470-476.
SWEA (Swedish Work Environment Authority). 2005. Cyanides, and hydrogen cyanides (as CN). Pp. 27 in Occupational Exposure Limit Values and Measures against Air Contaminants. AFS 2005:17 [online]. Available: http://www.av.se/dokument/inenglish/legislations/eng0517.pdf [accessed Nov. 20, 2014].
APPENDIX A
DERIVATION OF AGEL VALUES FOR CYANIDE SALTS
Derivation of AEGL-1 Values
The AEGL-1 values for hydrogen cyanide were used as target values for calculating the concentrations of the cyanide salt needed to generate the hydrogen cyanide AEGL values. The calculations assumed a temperature of 25°C, a pressure of 760 mm Hg, and complete hydrolysis (one mole of sodium cyanide or potassium cyanide will yield one mole of hydrogen cyanide, and one mole of calcium cyanide will yield two moles of hydrogen cyanide).
| Sodium Cyanide | |
| 10-min AEGL-1: | 2.5 ppm ÷ 1 = 2.5 ppm |
| 2.5 ppm × 49.0 ÷ 24.5 = 5.0 mg/m3 | |
| 30-min AEGL-1: | 2.5 ppm ÷ 1 = 2.5 ppm |
| 2.5 ppm × 49.0 ÷ 24.5 = 5.0 mg/m3 | |
| 1-h AEGL-1: | 2.0 ppm ÷ 1 = 2.0 ppm |
| 2.0 ppm × 49.0 ÷ 24.5 = 4.0 mg/m3 | |
| 4-h AEGL-1: | 1.3 ppm ÷ 1 = 1.3 ppm |
| 1.3 ppm × 49.0 ÷ 24.5 = 2.6 mg/m3 | |
| 8-h AEGL-1: | 1.0 ppm ÷ 1 = 1.0 ppm |
| 1.0 ppm × 49.0 ÷ 24.5 = 2.0 mg/m3 | |
| Potassium Cyanide | |
| 10-min AEGL-1: | 2.5 ppm ÷ 1 = 2.5 ppm |
| 2.5 ppm × 65.1 ÷ 24.5 = 6.6 mg/m3 | |
| 30-min AEGL-1: | 2.5 ppm ÷ 1 = 2.5 ppm |
| 2.5 ppm × 65.1 ÷ 24.5 = 6.6 mg/m3 | |
| 1-h AEGL-1: | 2.0 ppm ÷ 1 = 2.0 ppm |
| 2.0 ppm × 65.1 ÷ 24.5 = 5.3 mg/m3 | |
| 4-h AEGL-1: | 1.3 ppm ÷ 1 = 1.3 ppm |
| 1.3 ppm × 65.1 ÷ 24.5 = 3.5 mg/m3 | |
| 8-h AEGL-1: | 1.0 ppm ÷ 1 = 1.0 ppm |
| 1.0 ppm × 65.1 ÷ 24.5 = 2.7 mg/m3 | |
| Calcium Cyanide | |
| 10-min AEGL-1: | 2.5 ppm ÷ 2 = 1.25 ppm |
| 1.25 ppm × 92.1 ÷ 24.5 = 4.7 mg/m3 | |
| 30-min AEGL-1: | 2.5 ppm ÷ 2 = 1.25 ppm |
| 1.25 ppm × 92.1 ÷ 24.5 = 4.7 mg/m3 | |
| 1-h AEGL-1: | 2.0 ppm ÷ 2 = 1.0 ppm |
| 1.0 ppm × 92.1 ÷ 24.5 = 3.8 mg/m3 | |
| 4-h AEGL-1: | 1.3 ppm ÷ 2 = 0.65 ppm |
| 0.65 ppm × 92.1 ÷ 24.5 = 2.4 mg/m3 | |
| 8-h AEGL-1: | 1.0 ppm ÷ 2 = 0.50 ppm |
| 0.50 ppm × 92.1 ÷ 24.5 = 1.9 mg/m3 |
Derivation of AEGL-2 Values
The AEGL-2 values for hydrogen cyanide were used as target values for calculating the concentrations of the cyanide salt needed to generate the hydrogen cyanide AEGL values. The calculations assumed a temperature of 25°C, a pressure of 760 mm Hg, and complete hydrolysis (one mole of sodium cyanide or potassium cyanide will yield one mole of hydrogen cyanide, and one mole of calcium cyanide will yield two moles of hydrogen cyanide).
| Sodium Cyanide | |
| 10-min AEGL-2: | 17 ppm ÷ 1 = 17 ppm |
| 17 ppm × 49.0 ÷ 24.5 = 34 mg/m3 | |
| 30-min AEGL-2: | 10 ppm ÷ 1 = 10 ppm |
| 10 ppm × 49.0 ÷ 24.5 = 20 mg/m3 | |
| 1-h AEGL-2: | 7.1 ppm ÷ 1 = 7.1 ppm |
| 7.1 ppm × 49.0 ÷ 24.5 = 14 mg/m3 | |
| 4-h AEGL-2: | 3.5 ppm ÷ 1 = 3.5 ppm |
| 3.5 ppm × 49.0 ÷ 24.5 = 7.0 mg/m3 | |
| 8-h AEGL-2: | 2.5 ppm ÷ 1 = 2.5 ppm |
| 2.5 ppm × 49.0 ÷ 24.5 = 5.0 mg/m3 | |
| Potassium Cyanide | |
| 10-min AEGL-2: | 17 ppm ÷ 1 = 17 ppm |
| 17 ppm × 65.1 ÷ 24.5 = 45 mg/m3 |
| 30-min AEGL-2: | 10 ppm ÷ 1 = 10 ppm |
| 10 ppm × 65.1 ÷ 24.5 = 27 mg/m3 | |
| 1-h AEGL-2: | 7.1 ppm ÷ 1 = 7.1 ppm |
| 7.1 ppm × 65.1 ÷ 24.5 = 19 mg/m3 | |
| 4-h AEGL-2: | 3.5 ppm ÷ 1 = 3.5 ppm |
| 3.5 ppm × 65.1 ÷ 24.5 = 9.3 mg/m3 | |
| 8-h AEGL-2: | 2.5 ppm ÷ 1 = 2.5 ppm |
| 2.5 ppm × 65.1 ÷ 24.5 = 6.6 mg/m3 | |
| Calcium Cyanide | |
| 10-min AEGL-2: | 17 ppm ÷ 2 = 8.5 ppm |
| 8.5 ppm × 92.1 ÷ 24.5 = 32 mg/m3 | |
| 30-min AEGL-2: | 10 ppm ÷ 2 = 5 ppm |
| 5 ppm × 92.1 ÷ 24.5 = 19 mg/m3 | |
| 1-h AEGL-2: | 7.1 ppm ÷ 2 = 3.55 ppm |
| 3.55 ppm × 92.1 ÷ 24.5 = 13 mg/m3 | |
| 4-h AEGL-2: | 3.5 ppm ÷ 2 = 1.75 ppm |
| 1.75 ppm × 92.1 ÷ 24.5 = 6.6 mg/m3 | |
| 8-h AEGL-2: | 2.5 ppm ÷ 2 = 1.25 ppm |
| 1.25 ppm × 92.1 ÷ 24.5 = 4.7 mg/m3 |
Derivation of AEGL-3 Values
The AEGL-3 values for hydrogen cyanide were used as target values for calculating the concentrations of the cyanide salt needed to generate the hydrogen cyanide AEGL values. The calculations assumed a temperature of 25°C, a pressure of 760 mm Hg, and complete hydrolysis (one mole of sodium cyanide or potassium cyanide will yield one mole of hydrogen cyanide, and one mole of calcium cyanide will yield two moles of hydrogen cyanide).
| Sodium Cyanide | |
| 10-min AEGL-3: | 27 ppm ÷ 1 = 27 ppm |
| 27 ppm × 49.0 ÷ 24.5 = 54 mg/m3 | |
| 30-min AEGL-3: | 21 ppm ÷ 1 = 21 ppm |
| 21 ppm × 49.0 ÷ 24.5 = 42 mg/m3 | |
| 1-h AEGL-3: | 15 ppm ÷ 1 = 15 ppm |
| 15 ppm × 49.0 ÷ 24.5 = 30 mg/m3 | |
| 4-h AEGL-3: | 8.6 ppm ÷ 1 = 8.6 ppm |
| 8.6 ppm × 49.0 ÷ 24.5 = 17 mg/m3 | |
| 8-h AEGL-3: | 6.6 ppm ÷ 1 = 6.6 ppm |
| 6.6 ppm × 49.0 ÷ 24.5 = 13 mg/m3 | |
| Potassium Cyanide | |
| 10-min AEGL-3: | 27 ppm ÷ 1 = 27 ppm |
| 27 ppm × 65.1 ÷ 24.5 = 72 mg/m3 | |
| 30-min AEGL-3: | 21 ppm ÷ 1 = 21 ppm |
| 21 ppm × 65.1 ÷ 24.5 = 56 mg/m3 | |
| 1-h AEGL-3: | 15 ppm ÷ 1 = 15 ppm |
| 15 ppm × 65.1 ÷ 24.5 = 40 mg/m3 | |
| 4-h AEGL-3: | 8.6 ppm ÷ 1 = 8.6 ppm |
| 8.6 ppm × 65.1 ÷ 24.5 = 23 mg/m3 | |
| 8-h AEGL-3: | 6.6 ppm ÷ 1 = 6.6 ppm |
| 6.6 ppm × 65.1 ÷ 24.5 = 18 mg/m3 | |
| Calcium Cyanide | |
| 10-min AEGL-3: | 27 ppm ÷ 2 = 13.5 ppm |
| 13.5 ppm × 92.1 ÷ 24.5 = 51 mg/m3 | |
| 30-min AEGL-3: | 21 ppm ÷ 2 = 10.5 ppm |
| 10.5 ppm × 92.1 ÷ 24.5 = 39 mg/m3 | |
| 1-h AEGL-3: | 15 ppm ÷ 2 = 7.5 ppm |
| 7.5 ppm × 92.1 ÷ 24.5 = 28 mg/m3 | |
| 4-h AEGL-3: | 8.6 ppm ÷ 2 = 4.3 ppm |
| 4.3 ppm × 92.1 ÷ 24.5 = 16 mg/m3 | |
| 8-h AEGL-3: | 6.6 ppm ÷ 2 = 3.3 ppm |
| 3.3 ppm × 92.1 ÷ 24.5 = 12 mg/m3 |
APPENDIX B
DERIVATION OF THE AEGL VALUES FOR HYDROGEN CYANIDE (NRC 2002)
Derivation of AEGL-1 Values
| Key studies: | Leeser et al. 1990 |
| Supporting studies: | Hardy et al. 1950; Grabois 1954; Maehly and |
| Swensson 1970; El Ghawabi et al. 1975 | |
| Toxicity end point: | No adverse effect in healthy adult humans occupationally exposed at geometric mean concentration of ≤1 [range 0.01-3.3 ppm, personal samplers (up to 6 ppm, area samples)] or 5 ppm; mild headache in adult humans occupationally exposed at 8 ppm. The exposure duration was considered to be 8 h. |
| Uncertainty factor: | An uncertainty factor was not applied to the Leeser et al. (1990) 1-ppm concentration because it is the lowest NOAEL. A factor of 3 for intraspecies differences was applied to the supporting studies because no susceptible populations were identified. The uncertainty factor was applied to the 8-h 5 ppm and 8 ppm concentrations, which resulted in concentrations close to the 8-h 1-ppm concentration in the Leeser et al. (1990) study. |
| Time scaling: | C3 × t = k (conservative time-scaling relationship because, the relationship between concentration and exposure duration for the headache effect is unknown). An 8-h 1 ppm concentration was used as the starting point for time scaling. |
| Calculations: | (C3 ÷ uncertainty factors) × t = k |
| (1 ppm)3 × 480 min = 480 ppm-min | |
| 10-min AEGL-1: | (480 ppm-min/10 min)1/3 = 3.6 ppm Because 3.6 ppm is above the highest exposure concentration in the Leeser et al. (1990) study, as measured by personal monitors, the 10-min value was set equal to the 30-min value. |
| 30-min AEGL-1: | (480 ppm-min ÷ 30 min)1/3 = 2.5 ppm |
| 1-h AEGL-1: | (480 ppm-min ÷ 60 min)1/3 = 2.0 ppm |
| 4-h AEGL-1: | (480 ppm-min ÷ 240 min)1/3 = 1.3 ppm |
| 8-h AEGL-1: | 1.0 ppm |
| Derivation of AEGL-2 Values | |
| Key study: | Purser 1984 |
| Toxicity end point: | Slight central nervous system depression in monkeys inhaling 60 ppm for 30 min. |
| Time scaling: | C2 × t = k (this document; based on regression analysis of incapacitation and lethality data for the monkey) |
| Uncertainty factors: | 2 for interspecies differences |
| 3 for intraspecies variability | |
| Total uncertainty factor: 6 | |
| Calculations: | (C2 ÷ uncertainty factors) × t = k |
| (60 ppm ÷ 6)2 × 30 min = 3,000 ppm-min | |
| 10-min AEGL-2: | (3,000 ppm-min ÷ 10 min)½ = 17 ppm |
| 30-min AEGL-2: | 60 ppm ÷ 6 = 10 ppm |
| 1-h AEGL-2: | (3,000 ppm-min ÷ 60 min)½ = 7.1 ppm |
| 4-h AEGL-2: | (3,000 ppm-min ÷ 240 min)½ = 3.5 ppm |
| 8-h AEGL-2: | (3,000 ppm-min ÷ 480 min)½ = 2.5 ppm |
| Derivation of AEGL-3 Values | |
| Key study: | Haskell Laboratory 1981 |
| Toxicity end point: | 15-min LC01 of 138 ppm in the rat |
| 30-min LC01 of 127 ppm in the rat | |
| 1-h LC01 of 88 ppm in the rat | |
| LC01 derived by probit analysis | |
| Time scaling: | C2.6 × t = k (this document; based on the Haskell Laboratory [1981] rat dataset) |
| Uncertainty factors: | 2 for interspecies |
| 3 for intraspecies | |
| Total uncertainty factor: 6 | |
| Calculations: | (C2.6 ÷ uncertainty factors) × t = k |
| (138 ppm ÷ 6)2.6 × 15 min = 52,069.5 ppm-min | |
| (127 ppm ÷ 6)2.6 × 30 min = 83,911 ppm-min | |
| (88 ppm ÷ 6)2.6 × 60 min = 64,656.6 ppm-min | |
| 10-min AEGL-3: | (52,069.5 ppm-min ÷ 10 min)1/2.6 = 27 ppm |
| 30-min AEGL-3: | 127 ppm ÷ 6 = 21 ppm |
| 1-h AEGL-3: | 88 ppm ÷ 6 = 15 ppm |
| 4-h AEGL-3: | (64,656.6 ppm-min ÷ 240 min)1/2.6 = 8.6 ppm |
| 8-h AEGL-3: | (64,656.6 ppm-min ÷ 480 min)1/2.6 = 6.6 ppm |
APPENDIX C
ACUTE EXPOUSRE GUIDELINES FOR CYANIDE SALTS
Derivation Summary
AEGL-1 VALUES
| 10 min | 30 min | 1 h | 4 h | 8 h | |
| Sodium cyanide | |||||
| 5.0 mg/m3 | 5.0 mg/m3 | 4.0 mg/m3 | 2.6 mg/m3 | 2.0 mg/m3 | |
| Potassium cyanide | |||||
| 6.6 mg/m3 | 6.6 mg/m3 | 5.3 mg/m3 | 3.5 mg/m3 | 2.7 mg/m3 | |
| Calcium cyanide | |||||
| 4.7 mg/m3 | 4.7 mg/m3 | 3.8 mg/m3 | 2.4 mg/m3 | 1.9 mg/m3 | |
| Key reference: NRC (National Research Council). 2002. Hydrogen cyanide. Pp. 211-276 in Acute Exposure Guideline Levels for Selected Airborne Chemicals, Volume 2. Washington, DC: The National Academies Press. | |||||
| End point/Concentration/Rationale: AEGL-1 values for hydrogen cyanide were used to obtain AEGL-1 values for the three cyanide salts. The use of hydrogen cyanide as a surrogate for the cyanide salts is deemed appropriate because qualitative (clinical signs) and quantitative (adjusted rat oral LD50 values) data suggest that the cyanide moiety is responsible for the acute toxicity of the cyanide salts. The hydrogen cyanide AEGL-1 values were used as target values for calculating the concentrations of cyanide salt needed to generate the hydrogen cyanide AEGL values. The calculations assumed a temperature of 25°C, a pressure of 760 mm Hg, and complete hydrolysis. | |||||
| Molar adjustment factor: | |||||
| 1 (sodium cyanide and potassium cyanide); 2 (calcium cyanide) | |||||
| Data adequacy: AEGL-1 values for the cyanide salts were derived by analogy to the AEGL-1 values for hydrogen cyanide. The database on hydrogen cyanide is robust. The adjusted rat oral LD50 value for calcium cyanide is much greater than would be expected on a molar basis for cyanide (suggesting that it is a less toxic compound). However, the production of two moles of hydrogen cyanide was assumed per mole of calcium cyanide. That assumption will yield protective AEGL values. | |||||
AEGL-2 VALUES
| 10 min | 30 min | 1 h | 4 h | 8 h | |||
| Sodium cyanide | |||||||
| 34 mg/m3 | 0 mg/m3 | 14 mg/m3 | 7.0 mg/m3 | 5.0 mg/m3 | |||
| Potassium cyanide | |||||||
| 45 mg/m3 | 7 mg/m3 | 19 mg/m3 | 9.3 mg/m3 | 6.6 mg/m3 | |||
| Calcium cyanide | |||||||
| 32 mg/m3 | 9 mg/m3 | 13 mg/m3 | 6.6 mg/m3 | 4.7 mg/m3 | |||
| Key reference: NRC (National Research Council). 2002. Hydrogen cyanide. Pp. 211-276 in Acute Exposure Guideline Levels for Selected Airborne Chemicals, Volume 2. Washington, DC: The National Academies Press. | |||||||
AEGL-2 VALUES
| End point/Concentration/Rationale: AEGL-2 values for hydrogen cyanide were used to obtain AEGL-2 values for the three cyanide salts. The use of hydrogen cyanide as a surrogate for the cyanide salts is deemed appropriate because qualitative (clinical signs) and quantitative (adjusted rat oral LD50 values) data suggest that the cyanide moiety is responsible for acute toxicity of the cyanide salts. The hydrogen cyanide AEGL-2 values were used as target values for calculating the concentrations of cyanide salt needed to generate the hydrogen cyanide AEGL values. The calculations assumed a temperature of 25°C, a pressure of 760 mm Hg, and complete hydrolysis. | ||||
| Molar adjustment factor: | ||||
| 1 (sodium cyanide and potassium cyanide); 2 (calcium cyanide) | ||||
| Data adequacy: AEGL-2 values for the cyanide salts were derived by analogy to the AEGL-2 values for hydrogen cyanide. The database on hydrogen cyanide is robust. The adjusted rat oral LD50 value for calcium cyanide is much greater than would be expected on a molar basis for cyanide (suggesting that it is a less toxic compound). However, the production of two moles of hydrogen cyanide was assumed per mole of calcium cyanide. That assumption will yield protective AEGL values. | ||||
AEGL-3 VALUES
| 10 min | 30 min | 1 h | 4 h | 8 h |
| Sodium cyanide | ||||
| 54 mg/m3 | 42 mg/m3 | 30 mg/m3 | 17 mg/m3 | 13 mg/m3 |
| Potassium cyanide | ||||
| 72 mg/m3 | 56 mg/m3 | 40 mg/m3 | 23 mg/m3 | 18 mg/m3 |
| Calcium cyanide | ||||
| 51 mg/m3 | 39 mg/m3 | 28 mg/m3 | 16 mg/m3 | 12 mg/m3 |
| Key reference: NRC (National Research Council). 2002. Hydrogen cyanide. Pp. 211-276 in Acute Exposure Guideline Levels for Selected Airborne Chemicals, Volume 2. Washington, DC: The National Academies Press. | ||||
| End point/Concentration/Rationale: AEGL-3 values for hydrogen cyanide were used to obtain AEGL-3 values for the three cyanide salts. The use of hydrogen cyanide as a surrogate for the cyanide salts is deemed appropriate because qualitative (clinical signs) and quantitative (adjusted rat oral LD50 values) data suggest that the cyanide moiety is responsible for acute toxicity of the cyanide salts. The hydrogen cyanide AEGL-3 values were used as target values for calculating the concentrations of cyanide salt needed to generate the hydrogen cyanide AEGL values. The calculations assumed a temperature of 25°C, a pressure of 760 mm Hg, and complete hydrolysis. | ||||
| Molar adjustment factor: | ||||
| 1 (sodium cyanide and potassium cyanide) | ||||
| 2 (calcium cyanide) | ||||
| Data adequacy: AEGL-3 values for the cyanide salts were derived by analogy to the AEGL-3 values for hydrogen cyanide. The database on hydrogen cyanide is robust. The adjusted rat oral LD50 value for calcium cyanide is much greater than would be expected on a molar basis for cyanide (suggesting that it is a less toxic compound). However, the production of two moles of hydrogen cyanide was assumed per mole of calcium cyanide. That assumption will yield protective AEGL values. | ||||
APPENDIX D
ACUTE EXPOUSRE GUIDELINES FOR HYDROGEN CYANIDE
Derivation Summary (NRC 2002)
AEGL-1 VALUES FOR HYDROGEN CYANIDE
| 10 min | 30 min | 1 h | 4 h | 8 h |
| 10 min | 30 min | 1 h | 4 h | 8 h |
| 2.5 ppm | 2.5 ppm | 2.0 ppm | 1.3 ppm | 1.0 ppm |
| (2.8 mg/m3) | (2.8 mg/m3) | (2.2 mg/m3) | (1.4 mg/m3) | (1.1 mg/m3) |
| Key reference: Leeser, J.E., J.A. Tomenson, and D.D. Bryson. 1990. A Cross-sectional Study of the Health of Cyanide Salt Production Workers. Report No. OHS/R/2. ICI Central Toxicology Laboratory, Macclesfield, U.K. | ||||
| Supporting references: (1) El Ghawabi, S.H., M.A. Gaafar, A.A. El-Saharti, S.H. Ahmed, K.K. Malash, and R. Fares. 1975. Chronic cyanide exposure: A clinical, radioisotope, and laboratory study. Br.. J. Ind. Med. 32(3):215-219. | ||||
| (2) Grabois, B. 1954. Exposure to hydrogen cyanide in processing of apricot kernels. Monthly Review NY Department of Labor, 33(September):33-36. | ||||
| (3) Maehly, A.C., and A. Swensson. 1970. Cyanide and thiocyanate levels in blood and urine of workers with low-grade exposure to cyanide. Int. Arch. Arbeitsmed. 27(3):195-209. | ||||
| (4) Hardy, H.L., W.M. Jeffries, M.M. Wasserman, and W.R. Waddell. 1950. Thiocyanate effect following industrial cyanide exposure - report of two cases. New Engl. J. Med. 242(25):968-972. | ||||
| Test species/Strain/Number: | ||||
| Occupational exposures/63 employees, mean age 44.7 (Leeser et al. 1990) | ||||
| Occupational exposures/36 workers (El Ghawabi et al. 1975) | ||||
| Occupational exposures/five factories (Grabois 1954) | ||||
| Occupational exposures/94 workers (Maehly and Swensson 1970) | ||||
| Occupational exposures/factories (Hardy et al. 1950) | ||||
| Exposure route/Concentrations/Durations: Inhalation/geometric mean exposure of ≤1 ppm (range, 0.01-3.3 ppm; personal samplers), up to 6 ppm (area samples)/mean service years, 16.5 (Leeser et al. 1990); inhalation/average exposure 8 ppm/5-15 y (El Ghawabi et al. 1975); inhalation/5 ppm/unknown (Hardy et al. 1950; Grabois 1954; Maehly and Swensson 1970). | ||||
| Effects: No exposure related adverse symptoms or health effects (surveys and medical examinations taken in spring and fall of year) (Leeser et al. 1990); mild headache, other symptoms (El Ghawabi et al. 1975); no effects reported (Hardy et al. 1950; Grabois 1954; Maehly and Swensson 1970). | ||||
| End point/Concentration/Rationale: 1 ppm from the Leeser (1990) study; 8 ppm from the El Ghawabi et al. (1975) study; or 5 ppm from the Hardy et al. (1950), Grabois (1954), and Maehly and Swensson (1970) studies were considered no-adverse-effect to mild effect concentrations for an 8-h workday. The NRC adjusted the chronic 8 ppm value of El Ghawabi et al. (1975) to a 1-h exposure for healthy adults. | ||||
| Uncertainty Factors/Rationale: | ||||
| Total uncertainty factor: 3 | ||||
| Interspecies: Not applicable | ||||
| Intraspecies: 3, an uncertainty factor was not applied to the Leeser et al.(1990) 1 ppm concentration, as it is the lowest NOAEL. A factor of 3 was applied to the supporting studies as no specific susceptible populations were identified in monitoring studies or during the clinical use of nitroprusside solutions to control hypertension. The detoxifying enzyme rhodanese is present in all individuals including newborns. Application of the uncertainty factor to the El Ghawabi et al. (1975; as adjusted by the NRC) and Grabois (1954) data results in a value close to the 8-h 1 ppm concentration in the Leeser et al. (1990) study. | ||||
| Modifying factor: Not applicable | ||||
| Animal-to-human dosimetric Adjustment: Not applicable | ||||
| Time scaling: Because of the long-term exposure duration of the key studies, the conservative time-scaling value of n = 3 (k = 480 ppm3-min) was applied when scaling to shorter exposure durations. The starting point for time scaling was an 8-h concentration of 1 ppm. | ||||
| Data adequacy: The preponderance of data from the key studies supports an 8-h no-effect concentration of 1 ppm. The Leeser et al. (1990) study encompassed subjective symptoms as well as extensive medical examinations. The occupational monitoring study of El Ghawabi et al. (1975), in which it is believed that workers inhaling a mean concentration of 8 ppm may suffer mild headaches, supports the safety of the derived values. The values are also supported by a NIOSH (1976) report in which 5 ppm was identified as a no-effect concentration in the Grabois et al. (1954) occupational study. Additional monitoring studies support the values. | ||||
AEGL-2 VALUES FOR HYDROGEN CYANIDE
| 10 min | 30 min | 1 h | 4 h | 8 h |
| 17 ppm | 10 ppm | 7.1 ppm | 3.5 ppm | 2.5 ppm |
| (19 mg/m3) | (11 mg/m3) | (7.8 mg/m3) | (3.9 mg/m3) | (2.8 mg/m3) |
| Key references: (1) Purser, D.A. 1984. A bioassay model for testing the incapacitating effects of exposure to combustion product atmospheres using cynomolgus monkeys. J. Fire Sci. 2:20-36. | ||||
| (2) Purser, D.A., P. Grimshaw and K.R. Berrill. 1984. Intoxication by cyanide in fires: A study in monkeys using polyacrylonitrile. Arch. Environ. Health 39(6):393-400. | ||||
| Test species/Strain/Sex/Number: Cynomolgus monkeys, 4 per exposure group (sex not stated) | ||||
| Exposure route/Concentrations/Durations: Inhalation, 60, 100, 102, 123, 147, or 156 ppm for 30 min | ||||
| Effects: (30-min exposures) | ||||
| 60 ppm - increased respiratory minute volume and slight changes in EEGs near end of exposure | ||||
| 100 ppm - incapacitation (semi-conscious state) in 19 min | ||||
| 102 ppm - incapacitation in 16 min | ||||
| 123 ppm - incapacitation in 15 min | ||||
| 147 ppm - incapacitation in 8 min | ||||
| 156 ppm - incapacitation in 8 min | ||||
| End point/Concentration/Rationale: The 30-min exposure to 60 ppm, a NOAEL, was chosen because the next higher tested concentration, 100 ppm, resulted in incapacitation within the 30-min exposure period. | ||||
| Uncertainty factors/Rationale: | ||||
| Total uncertainty factor: 6 | ||||
| Interspecies: 2–The monkey is an appropriate model for humans, the small size and higher respiratory rate of the monkey may result in more rapid uptake and greater sensitivity than in humans. | ||||
| Intraspecies: 3–No specific susceptible populations were identified during monitoring studies or during the clinical use of nitroprusside solutions to control hypertension. The detoxifying enzyme rhodanese is present in all individuals including newborns. | ||||
| Modifying Factor: Not applicable | ||||
| Animal-to-human dosimetric adjustment: Insufficient data. | ||||
| Time scaling: Cn × t = k, where n = 2 and k = 3,000 ppm-min on the basis of regression analysis of time-concentration relationships for both incapacitation times of 8 to 19 min and lethality data (3-60 min) for the monkey. | ||||
| Data adequacy: Although human data are limited to primarily occupational monitoring studies, the data base on animal studies is good. The test atmosphere in the key study was supplied via a face mask to the restrained test subjects; restrained animals have been shown to be more sensitive than unrestrained animals to inhaled toxicants. | ||||
| Relative species sensitivity to inhaled HCN may be related to breathing rate. Compared to rodents, the slower breathing rate of humans and monkeys may make them less sensitive to the effects of HCN. | ||||
| The following two supporting studies were located: | ||||
| 1. A 30-min exposure of rats to 55 ppm resulted in changes in lung phospholipids and lung dynamics. Use of an uncertainty factor of 6 results in a 30-min AEGL-2 of 9.2 ppm, which is similar to the AEGL value. | ||||
| 2. Humans inhaling mean concentrations of 10 or 15 ppm in electroplating or silver-reclaiming factories for up to 15 y reported symptoms including headache, fatigue, effort dyspnea, and syncopes. There was no evidence that these symptoms occurred on the first day of employment. | ||||
AEGL-3 VALUES FOR HYDROGEN CYANIDE
| 10 min | 30 min | 1 h | 4 h | 8 h |
| 27 ppm | 21 ppm | 15 ppm | 8.6 ppm | 6.6 ppm |
| (30 mg/m3) | (23 mg/m3) | (17 mg/m3) | (9.7 mg/m3) | (7.3 mg/m3) |
| Key reference: Haskell Laboratory. 1981. Inhalation Toxicity of Common Combustion Gases. Haskell Laboratory Report No. 238-81. E.I. du Pont de Nemours and Company, Haskell Laboratory, Newark, DE. | ||||
| Test species/Strain/Sex/Number: Crl:CD male rats, 10/exposure group | ||||
| Exposure route/Concentrations/Durations: Inhalation | ||||
| 273, 328, 340, 353, 441, 493, or 508 ppm for 5 min | ||||
| 110, 175, 188, 204, 230, 251, 283, or 403 ppm for 15 min | ||||
| 128, 149, 160, 183, 222, or 306 ppm for 30 min | ||||
| 76, 107, 154, 183, or 222 ppm for 60 min | ||||
| Effects (LC01 values were calculated by Haskell Laboratory using probit analysis): | ||||
| 5-min LC01: 283 ppm | ||||
| 15-min LC01: 138 ppm | ||||
| 30-min LC01: 127 ppm | ||||
| 60-min LC01: 88 ppm | ||||
| End point/Concentration/Rationale: | ||||
| The LC01, the threshold for lethality, was used as the basis for the derivation of the | ||||
| AEGL-3. | ||||
| The 15-min LC01 was used to calculate the 10 min value; the 30-min LC01 was used for the | ||||
| 30-min value; and the 60-min LC01 was used to derive the 1-, 4- and 8-h AEGL-3 values. | ||||
| Uncertainty factors/Rationale: | ||||
| Total uncertainty factor: 6 | ||||
| Interspecies: 2 - LC50 values for the same exposure durations for several species (rat, mouse, and rabbit) were within a factor of approximately 1.5 of each other. Based on relative respiration rates, humans are expected to be less sensitive than rodents. The mechanism is the same for all species. | ||||
| Intraspecies: 3 - No specific susceptible populations were identified during monitoring studies or during the clinical use of nitroprusside solutions to control hypertension. The detoxifying enzyme rhodanese is present in all individuals, including newborns. | ||||
| Modifying factor: Not applicable | ||||
| Animal-to-human dosimetric adjustment: Insufficient data. | ||||
| Time scaling: Cn × t = k, where n = 2.6 was derived from empirical data and used in a regression analysis of time-concentration relationships for rat LC50 values conducted at time periods of 5, 15, 30, and 60 min in the key study. However, the 15-, 30-, and 60-min values were calculated directly from the empirical (LC01) data. The k value of 52,069.5 ppm2.6-min, based on the 15-min LC01, was used for the 10-min value and the k value of 64,656.6 ppm2.6-min, based on the 1-h LC01, was used for the 4- and 8-h AEGL-3 values. | ||||
| Data adequacy: The study was well conducted. The HCN concentrations were continuously monitored using infrared spectrophotometry and validated by gas chromatography. | ||||
| One supporting study was located: exposure of rats to 30 ppm for 24 h resulted in lung congestion but no deaths. Use of a total uncertainty factor of 6 and extrapolation across time to 30 min results in a 30-min AEGL-3 of 22 ppm which is similar to the derived value of 21 ppm. | ||||
