### 1

2

3

4

5

6

7 

# ACUTE EXPOSURE GUIDELINE LEVELS (AEGLs) 8 

# FOR SELECTED CYANIDE SALTS 9
10 

# PROPOSED 11 12 

## Sodium Cyanide (CAS No. 143-33-9) 13 

## NaCN 14

15 

## Potassium Cyanide (CAS No. 151-50-8) 16 

## KCN 17

18 

## Calcium Cyanide (CAS No. 592-01-8) 19 

## Ca(CN) 2 

### 20 21 22 23 24 25 26 27 28SELECTED CYANIDE SA LTS Proposed: 04-2009/ Page 2 of 38



### 1 

# ACUTE EXPOSURE GUIDELINE LEVELS (AEGLs) 2 

# FOR 3 

# SELECTED CYANIDE SALTS 4

5

6

7 

# PROPOSED 8
9 10 11 12 13 14 15 16 17 18 19
20

21

22
23 24 25 26 27SELECTED CYANIDE SA LTS Proposed: 04-2009/ Page 3 of 38



### PREFACE 1 2 Under the authority of the Federal Adviso ry Committee Act (FACA) P. L. 92-463 of 1972, 3 the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances 4 (NAC/AEGL Committee) has been esta blished to identify, review and interpret relevant toxicologic 5 and other scientific data and develop AEGLs for high priority , acutely toxic chemicals. 6
7 AEGLs represent threshold exposure limits for the general public a nd are applicable to 8 emergency exposure periods ranging from 10 minutes to 8 hours. Three levels

C AEGL-1, AEGL-2 9 and AEGL-3

Care developed for each of five exposure periods (10 and 30 minutes, 1 hour, 4 hours, 10 and 8 hours) and are distinguished by varying degrees of severity of toxic effects. The three AEGLs 11 are defined as follows: 12 13 AEGL-1 is the airborne concentration (expresse d as parts per million or milligrams per cubic 14 meter [ppm or mg/m 3 

### ]) of a substance above which it is predicted that the general population, 15 including susceptible individuals , could experience notable disc omfort, irritation, or certain 16 asymptomatic, non-sensory effects. However, the effects are not disablin g and are transient and 17 reversible upon cessation of exposure. 18 19 AEGL-2 is the airborne concentr ation (expressed as ppm or mg/m 3 

### ) of a substance above 20 which it is predicted that the ge neral population, including susceptible individuals , could experience 21 irreversible or other serious, long- lasting adverse health effects or an impaired ability to escape. 22 23 AEGL-3 is the airborne concentr ation (expressed as ppm or mg/m 3 

### ) of a substance above 24 which it is predicted that the ge neral population, including susceptible individuals , could experience 25 life-threatening health effects or death. 26 27 Airborne concentrations below the AEGL-1 re present exposure levels that could produce 28 mild and progressively increasing but transient and nondisabling odor, ta ste, and sensory irritation or 29 certain asymptomatic, non-sensory effects. With increasing airborne conc entrations above each 30 AEGL, there is a progressive incr ease in the likelihood of occurrenc e and the severity of effects 31 described for each corresponding AEGL. Although the AEGL values represent threshold levels for 32 the general public, including sus ceptible subpopulations, such as infants, children, the elderly, 33 persons with asthma, and those with other illnesse s, it is recognized that individuals, subject to 34 unique or idiosyncratic responses, could experience the effects descri bed at concentrations below the 35 corresponding AEGL 36 37 38SELECTED CYANIDE SA LTS Proposed: 04-2009/ Page 4 of 38



### TABLE OF CONTENTS 1

LIST OF TABLES ................................................................................................................ 6 2

1. INTRODUC TION........................................................................................................... 8 3

2. HUMAN TOXICITY DATA .......................................................................................... 10 4

3. ANIMAL TOXICI TY DAT A.......................................................................................... 10 5

4. SPECIAL CONSID ERATIONS ................................................................................... 10 6

4.1. Metabolism and Disposit ion ..................................................................................................... .........................10 

### 7

4.2. Mechanism of Toxicity.......................................................................................................... .............................10 

### 8

4.3. Structure Activity Relationships............................................................................................... ........................10 

### 9

5. DATA ANALYSIS FO R AEGL -1 ................................................................................ 11 10

5.1. Summary of Human Data Relevant to AEGL-1....................................................................................... .......11 

### 11

5.2. Summary of Animal Data Relevant to AEGL-1 ...................................................................................... ........11 

### 12

5.3. Derivation of AEGL-1........................................................................................................... .............................11 

### 13

6. DATA ANALYSIS FO R AEGL -2 ................................................................................ 12 14

6.1. Summary of Human Data Relevant to AEGL-2....................................................................................... .......12 

### 15

6.2. Summary of Animal Data Relevant to AEGL-2 ...................................................................................... ........12 

### 16

6.3. Derivation of AEGL-2........................................................................................................... .............................12 

### 17

7. DATA ANALYSIS FO R AEGL -3 ................................................................................ 13 18

7.1. Summary of Human Data Relevant to AEGL-3....................................................................................... .......13 

### 19

7.2. Summary of Animal Data Relevant to AEGL-3 ...................................................................................... ........13 

### 20

7.3. Derivation of AEGL-3........................................................................................................... .............................13 

### 21

8. SUMMARY OF AEGLS .............................................................................................. 14 22

8.1. AEGL Values and To xicity Endpoints ............................................................................................. ................14 

### 23

8.2. Comparison with Other St andards and Guidelines ................................................................................. .......14 

### 24

8.3. Data Adequacy and Research Needs ............................................................................................... .................17 

### 25SELECTED CYANIDE SA LTS Proposed: 04-2009/ Page 5 of 38



### 9. REFERENC ES............................................................................................................ 18 1

APPENDIX A: DERIVATION OF AE GL VALUES FOR CY ANIDE SA LTS ..................... 20 2

APPENDIX B: TIME SCALING CALCULAT ION FOR HYDROGEN CYANIDE AEGL-1, 3 AEGL-2, AND AEGL-3 ...................................................................................................... 24 4

APPENDIX C: DERIVATION SUMMARY T ABLES FOR CYANIDE SALTS AEGLS...... 28 5

APPENDIX D: DERIVATION SUMMARY TABLES FOR HYDR OGEN CYANIDE .......... 32 6

APPENDIX E: CATEGORY PLOT S FOR CYANID E SALT S........................................... 36 7 8SELECTED CYANIDE SA LTS Proposed: 04-2009/ Page 6 of 38



### LIST OF TABLES 1 2
TABLE 1. CHEMICAL AND PHYSICAL PROPERTIES FOR SO DIUM CYAN IDE.............................................9 

### 3
TABLE 2. CHEMICAL AND PHYSICAL PR OPERTIES FOR POTA SSIUM CYANIDE .....................................9 

### 4
TABLE 3. CHEMICAL AND PHYSICAL PROPERTIES FOR CALCIUM CYANIDE..........................................9 

### 5
TABLE 4. RAT ORAL LETHALIT Y DATA.............................................................................................. .................11 

### 6
TABLE 5. AEGL-1 VALUES FOR CYANIDE SALTS* ...................................................................................... .......12 

### 7
TABLE 6. AEGL-2 VALUES FOR CYANIDE SALTS* ...................................................................................... .......12 

### 8
TABLE 7. AEGL-3 VALUES FOR CYANIDE SALTS* ...................................................................................... .......13 

### 9
TABLE 8. AEGL VALUES FOR METAL CYANID E SALTS* .................................................................................1 4 

### 10
TABLE 9. EXTANT STANDARDS AND GU IDELINES FOR SODI UM CYANIDE ..............................................14 

### 11
TABLE 10. EXTANT STANDARDS AND GU IDELINES FOR POTA SSIUM CYANIDE.....................................15 

### 12
TABLE 11. EXTANT STANDARDS AND GU IDELINES FOR CALCI UM CYANIDE.........................................16 

### 13SELECTED CYANIDE SA LTS Proposed: 04-2009/ Page 7 of 38



### SUMMARY 1 2 Sodium cyanide, potassium cyanide, and calcium cyanide are all simple inorganic cyanide salts 3 with an almond-like odor. They ma y react with water or moist air to release toxic, corrosive, or 4 flammable gases. Reaction with water may generate heat which will increase the concentration of 5 HCN fumes in the air (HSDB, 2008a, b, c). 6
7 Even though the salts are solids, inhalation of dus ts may result in ionization in the nasal or lung 8 mucosal fluids to yield CN - 

### . The salts may also react with water in humid air and be inhaled as 9 HCN. In both cases, there will be systemic abso rption of cyanide ion, which is the toxic moiety. 10 Cyanide inhibits cellular respiration by blocking electron transfer from cytochrome oxidase to 11 oxygen, causing tissue hypoxia and cell death. Low levels or low dose rates of cyanide are tolerated 12 by detoxicficaton by rhodanese to thiosulfate (Cohrssen, 2001). 13 14 In the absence of appropriate chemical-specific data for the title cyanides, the AEGL-1, AEGL-2, 15 and AEGL-3 values for hydrogen cyanide (NRC, 2002) will be used to obtain AEGL-1, AEGL-2, 16 and AEGL-3 values, respectively for the title cy anide salts. The use of hydrogen cyanide as a 17 surrogate for the cyanide salts is deemed appropr iate because qualitative (clinical signs) and 18 quantitative (adjusted rat oral LD 50 

### values) data suggest that the cy anide moiety is responsible for 19 acute toxicity of the cyanide salts. The hydrogen cyan ide AEGL values will be used as target values 20 for calculating the concentrations of cyanide salt needed to generate the hydrogen cyanide AEGL 21 values. Calculations assume 25 degrees C and 760 mm Hg and complete hydrolysis (one mole of 22 NaCN and KCN will yield one mole of HCN, and one mole of Ca(CN) 2 

### will yield two moles of 23 HCN). 24 25 26 The calculated values are listed in the table below. 27 28
AEGL VALUES FOR METAL CYANIDE SALTS*

Compound Classification 10-min 30-min 1-hr 4-hr 8-hr

AEGL-1 5.0 mg/m 3 5.0 mg/m 3 4.0 mg/m 3 2.6 mg/m 3 2.0 mg/m 3

AEGL-2 34 mg/m 3 20 mg/m 3 14 mg/m 3 7.0 mg/m 3 5.0 mg/m 3 Sodium Cyanide
AEGL-3 54 mg/m 3 42 mg/m 3 30 mg/m 3 17 mg/m 3 13 mg/m 3

AEGL-1 6.6 mg/m 3 6.6 mg/m 3 5.3 mg/m 3 3.5 mg/m 3 2.7 mg/m 3

AEGL-2 45 mg/m 3 27 mg/m 3 19 mg/m 3 9.3 mg/m 3 6.6 mg/m 3 Potassium Cyanide
AEGL-3 72 mg/m 3 56 mg/m 3 40 mg/m 3 23 mg/m 3 18 mg/m 3

AEGL-1 4.7 mg/m 3 4.7 mg/m 3 3.8 mg/m 3 2.4 mg/m 3 1.9 mg/m 3

AEGL-2 32 mg/m 3 19 mg/m 3 13 mg/m 3 6.6 mg/m 3 4.7 mg/m 3 Calcium Cyanide**
AEGL-3 51 mg/m 3 39 mg/m 3 28 mg/m 3 16 mg/m 3 12 mg/m 3

3⁄4 *These airborne concentrations will produce the equivalent AEGL values for hydrogen cyanide. 

### 29

3⁄4 ** Although the adjusted rat oral LC value for calcium cyanide is much greater (suggesting a less toxic 

### 30 compound) than would be expected on a molar basis for CN, the production of two moles of HCN was 

### 31 assumed per mole of calcium cyanide. This assumption will yield protective AEGL values. 

### 32SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 8 of 38



### 1. INTRODUCTION 1 2 Sodium cyanide, potassium cyanide, and calcium cyanide are all simple inorganic cyanide salts 3 with an almond-like odor. They ma y react with water or moist air to release toxic, corrosive, or 4 flammable gases. Reaction with water may generate heat which will increase the concentration of 5 HCN fumes in the air (HSDB, 2008a, b, c). 6
7 Even though the salts are solids, inhalation of dus ts may result in ionization in the nasal or lung 8 mucosal fluids to yield CN - 

### . The salts may also react with water in humid air and be inhaled as 9 HCN. In both cases, there will be systemic abso rption of cyanide ion, which is the toxic moiety. 10 Cyanide inhibits cellular respiration by blocking electron transfer from cytochrome oxidase to 11 oxygen, causing tissue hypoxia and cell death. Low levels or low dose rates of cyanide are tolerated 12 by detoxification by rhodanese to thiosulfate (Cohrssen, 2001). 13 14 Although hydrolysis rates were not located for the title cyanides, the rate of cyanide generation 15 may be dependent on ambient temperature and humidity and the chemical structure of the cyanide. 16 Hydrolysis reactions are as fo llows (Kirk-Othmer, 2008): 17 18 19 Sodium Cyanide and Potassium Cyanide: 20 One mole of sodium cyanide or potassium cyanide may react with water or moisture to produce a 21 maximum of one mole of hydrogen cyanide as follows: 22 23 NaCN + H 2 

### O 6 HCN + NaOH 24 25 KCN+ H 2 

### O 6 HCN + KOH 26
27 Calcium Cyanide: 28 One mole of calcium cyanide may react with wa ter or moisture to produce a maximum of two 29 moles of hydrogen cyanide as follows: 30 31 Ca(CN) 2 

### + 2H 2 

### O 6 2HCN + Ca(OH) 2 

### 32
33 34 Sodium cyanide is a white crystalline solid, a nd may be prepared by heating sodium amide 35 with carbon or by melting sodium chloride and calcium cyanamide together in an electric furnace. It 36 is used for extracting gold and s ilver from ores, heat treating of metals, electroplating, various 37 organic reactions, and the manu facturing of adipon itrile (Cohrssen, 2001). U.S. production was 38 reported as “at least” 1.14 x 10 11 

### grams in 1978, and U.S imports were reported as 2.77 x 10 7 

### pounds 39 in 1986 (HSDB, 2008a). 40 41 Potassium cyanide, a white crystalline solid, is prepared by reaction of an aqueous solution of 42 potassium hydroxide with hydrogen cyan ide. It is used for fine s ilver plating, dye s and speciality 43 products, and fumigation of fruit trees, ships, railway cars, and ware houses. U.S. production 44 information was not available; however, U.S. imports were reported as 1,468,423 pounds in 1987 45 (HSDB, 2008b). 46 47 Calcium cyanide is a white powder, and is pr epared from lime, calcium oxide, coke, and 48 nitrogen in an electric furnace. The commercial product is dark gray because of the presence of 49SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 9 of 38



### carbon. It is used in the extraction of precious metal ores, adsorption of gold complexes on carbon, 1 as a fumigant, and a rodenticide (Cohrssen, 2001). U.S. production information was not available; 2 however, U.S. imports were reported as 468,246 pounds in 1986 (HSDB, 2008c). 3 4
5 Available physicochemical data for the title cy anides are presented in Tables 1, 2, and 3. 6
7
TABLE 1. Chemical and Physical Properties for Sodium Cyanide

Parameter Value References

Synonyms Cyanogran; Cyanide of sodium; Cymag; Hydrocyanic acid sodium salt; Cyanobrik; White cyanide Cohrssen, 2001

Chemical formula NaCN HDSB, 2008a Molecular weight 49.0 HSDB, 2008a CAS Reg. No. 143-33-9 HSDB, 2008a Physical state White crystalline solid HSDB, 2008a Solubility in water 48 g/100 mL water at 10°C; forms HCN HSDB, 2008a Density /specific gravity 1.595 g/cu cm at 20 °C HSDB, 2008a Vapor pressure 1 mm Hg at 817 °C HSDB, 2008a Melting point 563 °C HSDB, 2008a Boiling point 1496 °C HSDB, 2008a

Conversion factors 1 ppm = 2.0 mg/m 3 1 mg/m 3 = 0.50 ppm


### 8
TABLE 2. Chemical and Physical Pr operties for Potassium Cyanide

Parameter Value References Synonyms Hydrocyanic acid potassium salt Cohrssen, 2001 Chemical formula KCN HDSB, 2008b Molecular weight 65.11 HSDB, 2008b CAS Reg. No. 151-50-8 HSDB, 2008b Physical state White crystalline solid HSDB, 2008b

Solubility in water 100 g/100 mL water at >176°F; forms HCN HSDB, 2008b

Density /specific gravity 1.55 at 20 °C HSDB, 2008b Melting point 634 °C HSDB, 2008b

Conversion factors 1 ppm = 2.7 mg/m 3 1 mg/m 3 = 0.38 ppm


### 9
TABLE 3. Chemical and Physical Pr operties for Calcium Cyanide

Parameter Value References

Synonyms Calcyanide; Cyanogas; Black Cyanide, aero; Calcium cyan ide, tech grade Cohrssen, 2001

Chemical formula Ca (CN) 2 HDSB, 2008c Molecular weight 92.12 HSDB, 2008c CAS Reg. No. 592-01-8 HSDB, 2008c Physical state White po wder, solid HSDB, 2008c

Solubility in water “Soluble in water with gradual liberation of HCN” HSDB, 2008c

Density /specific gravity 1.853 at 20 °C HSDB, 2008c

Melting point 640 °C (Estimated by extrapolation because of decomposition) HSDB, 2008c

Conversion factors 1 ppm = 3.8 mg/m 3SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 10 of 38

1 mg/m 3 = 0.27 ppm


### 1 2 3 2. HUMAN TOXICITY DATA 4
5 No human inhalation toxicity data were locate d for sodium, potassium, or calcium cyanide. 6 There are numerous reports of occupational e xposure to hydrogen cyan ide; these data are 7 summarized in the AEGL Technical Support Document for hydrogen cyanide (NRC, 2002). 8 9 3. ANIMAL TOXICITY DATA 10 11 No animal inhalation toxicity data were loca ted for sodium, potassium, or calcium cyanide. 12 However, the inhalation toxicity data base for hydr ogen cyanide is robust. Lethality data exist for 13 dogs, rats, mice and rabbits, and non-lethal toxicity data exist for nonhuman primates, rats, and mice. 14 These data are summarized in the AEGL Tec hnical Support Document for hydrogen cyanide (NRC, 15 2002). 16 17 18 4. SPECIAL CONSIDERATION S 19 4.1. Metabolism and Disposition 20 21 Solid cyanide salts deposited on moist respiratory tract surf aces may hydrolyze and release 22 absorbable cyanide. Another scenario would invo lve atmospheric hydrolysis of metal cyanides to 23 hydrogen cyanide vapor. Metabolism and dis position information for hydrogen cyanide is 24 summarized in the AEGL Technical Support Document for hydrogen cyanide (NRC, 2002). 25 26 4.2. Mechanism of Toxicity 27 28 HCN is a systemic poison that acts on the cen tral nervous system. HCN interrupts cellular 29 respiration by blocking electron transfer from cy tochrome oxidase to oxygen. Tissue oxygen levels 30 rise, resulting in increased ti ssue oxygen tension and decreased unloading for oxyhemoglobin. As a 31 consequence, oxidative metabolism may slow to a point where it cannot meet metabolic demands. 32 This is particularly critical in the brainstem nucle i where lack of an energy source results in central 33 respiratory arrest and death. Cyan ide can inhibit many other enzymes, particularly those that contain 34 iron or copper, but cytochrome oxidase appears to be the most sensitive enzyme. Cyanide also 35 stimulates the chemoreceptors of the carotid and aortic bodies to produce a brief period of 36 hyperpnea. Cardiac irregularities may occur, but death is due to respiratory arrest (Cohrssen, 2001; 37 Smith 1996). Brain lesions have been associated w ith exposure of animals to high concentrations of 38 HCN (ATSDR 1997). 39 40
41 4.3. Structure Activity Relationships 42 43 As previously stated, there are no human or anim al acute inhalation toxic ity data for the title 44 cyanide salts. However, acute oral toxicity da ta suggest both qualitative ly (clinical signs) and 45 quantitatively (rat LD 50 

### values) that the cyanide moiety is responsible for acute toxicity of the 46 cyanide salts. Cyanide-induced cl inical effects are indistinguisha ble following inhalation or dermal 47 exposure to HCN vapor, or oral e xposure to the cyanide salts Na CN and KCN, for both humans and 48SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 11 of 38



### animals. Clinical signs include headaches, dizzi ness, nausea, inability to concentrate, thoracic 1 oppression, palpitation, numbness, weakness, rapid pulse, face flus hing, unconsciousness, and death 2 (Cohrssen, 2001). 3 4
5 Rat oral LD 50 

### values support the conten tion that CN is the toxic moiety. These reported 6 values and LD values adjusted for CN are presented in Table 4. The CN adjusted values for 7 hydrogen, sodium, and potassium cyanides are co mparable; whereas, the adjusted value for 8 calcium cyanide is much greater (suggesting a le ss toxic compound) than would be expected on a 9 molar basis for CN. This may be due to a slow er hydrolysis rate, allowing for more efficient 10 detoxification, relative to the other cyanide salts. [Although hydrolysis rates were not located, 11 water solubility/reactivity is described as “f orms hydrogen cyanide” for sodium and potassium 12 cyanides (HSDB, 2008a; 2008b), an d “gradually liberates hydr ogen cyanide” for calcium 13 cyanide (HSDB, 2008c)]. 14 15 TABLE 4. Rat oral lethality data

Compound LD 50 (mg/kg) Adjusted LD 50 (mg/kg CN) Reference

HCN 8.5 8.2 Cohrssen, 2001 NaCN 15 7.9 Smyth et al., 1969 KCN 16 6.4 IUCLID, 2000 Ca(CN) 2 39 22 Smyth et al., 1969 

### 16 17 18 5. DATA ANALYSIS FOR AEGL-1 19 5.1. Summary of Human Data Relevant to AEGL-1 20 21 No human data relevant to developmen t of AEGL-1 values were identified. 22 23 5.2. Summary of Animal Data Relevant to AEGL-1 24 25 No animal data relevant to developm ent of AEGL-1 values were identified. 26 27 5.3. Derivation of AEGL-1 28 29 In the absence of appropriate chemical-speci fic data for the title cyanides, the AEGL-1 30 values for hydrogen cyanide (NRC, 2002) will be used to obtain AEGL-1 values for the title cyanide 31 salts. The use of hydrogen cyanide as a surrogate for the cyanide salts is deemed appropriate 32 because qualitative (clinical signs) a nd quantitative (adjusted rat oral LD 50 

### values) data suggest that 33 the cyanide moiety is responsible for acute toxicity of the cyanide salts. The hydrogen cyanide 34 AEGL-1 values will be used as target values fo r calculating the concentrations of cyanide salt 35 needed to generate the hydrogen cyanide AEGL va lues. Calculations assume 25 degrees C and 760 36 mm Hg and complete hydrolysis. The AEGL-1 valu es for the cyanide salts are given in Table 5, 37 calculations for these values are presented in Appendix A, and derivation summary tables for 38 cyanide salts are in Appendix C. [For comparis on, the calculations and derivation summary tables 39 for hydrogen cyanide AEGL values are presented in Appendix B and Appendix D, respectively.] 40
41SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 12 of 38

TABLE 5. AEGL-1 VALUES FOR CYANIDE SALTS*

Compound 10-min 30-min 1-hr 4-hr 8-hr

Sodium Cyanide 5.0 mg/m 3 5.0 mg/m 3 4.0 mg/m 3 2.6 mg/m 3 2.0 mg/m 3

Potassium Cyanide 6.6 mg/m 3 6.6 mg/m 3 5.3 mg/m 3 3.5 mg/m 3 2.7 mg/m 3

Calcium Cyanide** 4.7 mg/m 3 4.7 mg/m 3 3.8 mg/m 3 2.4 mg/m 3 1.9 mg/m 3

3⁄4 *These airborne concentrations will produce the equivalent AEGL values for hydrogen cyanide. 

### 1

3⁄4 ** Although the adjusted rat oral LC value for calcium cyanide is much greater (suggesting a less toxic 

### 2 compound) than would be expected on a molar basis for CN, the production of two moles of HCN was 

### 3 assumed per mole of calcium cyanide. This assumption will yield protective AEGL values. 

### 4 5 6
7 6. DATA ANALYSIS FOR AEGL-2 8 6.1. Summary of Human Data Relevant to AEGL-2 9 10 No human data relevant to developmen t of AEGL-2 values were identified. 11 12 6.2. Summary of Animal Data Relevant to AEGL-2 13 14 No animal data relevant to developm ent of AEGL-2 values were identified. 15 16 6.3. Derivation of AEGL-2 17 18 In the absence of appropriate chemical-speci fic data for the title cyanides, the AEGL-2 19 values for hydrogen cyanide (NRC, 2002) will be used to obtain AEGL-2 values for the title cyanide 20 salts. The use of hydrogen cyanide as a surrogate for the cyanide salts is deemed appropriate 21 because qualitative (clinical signs) a nd quantitative (adjusted rat oral LD 50 

### values) data suggest that 22 the cyanide moiety is responsible for acute toxicity of the cyanide salts. The hydrogen cyanide 23 AEGL-2 values will be used as target values fo r calculating the concentrations of cyanide salt 24 needed to generate the hydrogen cyanide AEGL va lues. Calculations are for 25 degrees C and 760 25 mm Hg and assume complete hydrolysis. The AEGL -2 values for the cyanide salts are given in 26 Table 6, calculations for these values are presen ted in Appendix A, and derivation summary tables 27 for cyanide salts are in Appendix C. [For co mparison, the calculations and derivation summary 28 tables for hydrogen cyanide AEGL values ar e presented in Appendix B and Appendix D, 29 respectively.] 30 31 32

TABLE 6. AEGL-2 VALUES FOR CYANIDE SALTS*

Compound 10-min 30-min 1-hr 4-hr 8-hr

Sodium Cyanide 34 mg/m 3 20 mg/m 3 14 mg/m 3 7.0 mg/m 3 5.0 mg/m 3

Potassium Cyanide 45 mg/m 3 27 mg/m 3 19 mg/m 3 9.3 mg/m 3 6.6 mg/m 3

Calcium Cyanide** 32 mg/m 3 19 mg/m 3 13 mg/m 3 6.6 mg/m 3 4.7 mg/m 3

3⁄4 *These airborne concentrations will produce the equivalent AEGL values for hydrogen cyanide. 

### 33SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 13 of 38

3⁄4 ** Although the adjusted rat oral LC value for calcium cyanide is much greater (suggesting a less toxic 

### 1 compound) than would be expected on a molar basis for CN, the production of two moles of HCN was 

### 2 assumed per mole of calcium cyanide. This assumption will yield protective AEGL values. 

### 3 4
5 6 7. DATA ANALYSIS FOR AEGL-3 7 7.1. Summary of Human Data Relevant to AEGL-3 8 9 No human data relevant to developmen t of AEGL-3 values were identified. 10
11 7.2. Summary of Animal Data Relevant to AEGL-3 12 13 No animal data relevant to developm ent of AEGL-3 values were identified. 14 15 16 7.3. Derivation of AEGL-3 17 18 In the absence of appropriate chemical-speci fic data for the title cyanides, the AEGL-3 19 values for hydrogen cyanide (NRC, 2002) will be used to obtain AEGL-3 values for the title cyanide 20 salts. The use of hydrogen cyanide as a surrogate for the cyanide salts is deemed appropriate 21 because qualitative (clinical signs) a nd quantitative (adjusted rat oral LD 50 

### values) data suggest that 22 the cyanide moiety is responsible for acute toxicity of the cyanide salts. The hydrogen cyanide 23 AEGL-3 values will be used as target values fo r calculating the concentrations of cyanide salt 24 needed to generate the hydrogen cyanide AEGL va lues. Calculations are for 25 degrees C and 760 25 mm Hg and assume complete hydrolysis. The AEGL -3 values for the cyanide salts are given in 26 Table 7, calculations for these values are presen ted in Appendix A, and derivation summary tables 27 for cyanide salts are in Appendix C. [For co mparison, the calculations and derivation summary 28 tables for hydrogen cyanide AEGL values ar e presented in Appendix B and Appendix D, 29 respectively.] 30 31 32

TABLE 7. AEGL-3 VALUES FOR CYANIDE SALTS*

Compound 10-min 30-min 1-hr 4-hr 8-hr

Sodium Cyanide 54 mg/m 3 42 mg/m 3 30 mg/m 3 17 mg/m 3 13 mg/m 3

Potassium Cyanide 72 mg/m 3 56 mg/m 3 40 mg/m 3 23 mg/m 3 18 mg/m 3

Calcium Cyanide** 51 mg/m 3 39 mg/m 3 28 mg/m 3 16 mg/m 3 12 mg/m 3

3⁄4 *These airborne concentrations will produce the equivalent AEGL values for hydrogen cyanide. 

### 33

3⁄4 ** Although the adjusted rat oral LC value for calcium cyanide is much greater (suggesting a less toxic 

### 34 compound) than would be expected on a molar basis for CN, the production of two moles of HCN was 

### 35 assumed per mole of calcium cyanide. This assumption will yield protective AEGL values. 

### 36 37 38SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 14 of 38



### 8. SUMMARY OF AEGLS 1 8.1. AEGL Values and Toxicity Endpoints 2 3 AEGL values are summarized in Table 8. AEGL values were based on molar adjustments of 4 hydrogen cyanide AEGL values. 5 6

TABLE 8. AEGL VALUES FOR ME TAL CYANIDE SALTS*

Compound Classification 10-min 30-min 1-hr 4-hr 8-hr

AEGL-1 5.0 mg/m 3 5.0 mg/m 3 4.0 mg/m 3 2.6 mg/m 3 2.0 mg/m 3

AEGL-2 34 mg/m 3 20 mg/m 3 14 mg/m 3 7.0 mg/m 3 5.0 mg/m 3 Sodium Cyanide
AEGL-3 54 mg/m 3 42 mg/m 3 30 mg/m 3 17 mg/m 3 13 mg/m 3

AEGL-1 6.6 mg/m 3 6.6 mg/m 3 5.3 mg/m 3 3.5 mg/m 3 2.7 mg/m 3

AEGL-2 45 mg/m 3 27 mg/m 3 19 mg/m 3 9.3 mg/m 3 6.6 mg/m 3 Potassium Cyanide
AEGL-3 72 mg/m 3 56 mg/m 3 40 mg/m 3 23 mg/m 3 18 mg/m 3

AEGL-1 4.7 mg/m 3 4.7 mg/m 3 3.8 mg/m 3 2.4 mg/m 3 1.9 mg/m 3

AEGL-2 32 mg/m 3 19 mg/m 3 13 mg/m 3 6.6 mg/m 3 4.7 mg/m 3 Calcium Cyanide**
AEGL-3 51 mg/m 3 39 mg/m 3 28 mg/m 3 16 mg/m 3 12 mg/m 3

3⁄4 *These airborne concentrations will produce the equivalent AEGL values for hydrogen cyanide. 

### 7

3⁄4 ** Although the adjusted rat oral LC value for calcium cyanide is much greater (suggesting a less toxic 

### 8 compound) than would be expected on a molar basis for CN, the production of two moles of HCN was 

### 9 assumed per mole of calcium cyanide. This assumption will yield protective AEGL values. 

### 10 11 12 13 8.2. Comparison with Other St andards and Guidelines 14 15

TABLE 9. Extant Standards and Gu idelines for Sodium Cyanide

Exposure Duration Guideline 10 min 30 min 1 h 4 h 8 h AEGL-1 5.0 mg/m 3 5.0 mg/m 3 4.0 mg/m 3 2.6 mg/m 3 2.0 mg/m 3 AEGL-2 34 mg/m 3 20 mg/m 3 14 mg/m 3 7.0 mg/m 3 5.0 mg/m 3 AEGL-3 54 mg/m 3 42 mg/m 3 30 mg/m 3 17 mg/m 3 13 mg/m 3

PEL-TWA (OSHA) a 5.0 mg/m 3 (as CN) IDLH (NIOSH) b 25 mg/m 3 (as CN) REL-TWA (NIOSH) c 5.0 mg/m 3 (as CN)[10-min] TLV-STEL (ACGIH) d 5.0 mg/m 3 (as CN) MAK (Germany) e 3.8 mg/m 3 MAC-Peak Category (The Netherlands) f 5.0 mg/m 3 (as CN) OEL (Sweden) g 5.0 mg/m 3 (as CN)

a OSHA PEL-TWA (Occupationa l Health and Safety Administration, Permissible Exposure Limits - Time Weighted 

### 16 Average) (OSHA, 1993) is defined analogous to the ACGIH-TLV-TWA, but is for exposures of no more than 10 

### 17 hours/day, 40 hours/week. Va lue for cyanides (as CN). 

### 18SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 15 of 38



### 1

b IDLH (Immediately Dangerous to Life and Health, National Institute of Occupational Safety and Health) (NIOSH, 

### 2 1996) represents the maximum concentration from whic h one could escape within 30 minutes without any 

### 3 escape-impairing symptoms, or any irreversible health effects. Value for cyanides (as CN). 

### 4 5

c NIOSH REL-TWA (National Institute of Occupational Safe ty and Health, Recommended Exposure Limits - Time 

### 6 Weighted Average) (NIOSH, 2005) is defined analogous to the ACGIH-TL V-TWA. Value for cyanides except 

### 7 hydrogen cyanide. 

### 8 9

d ACGIH TLV-STEL (Threshold Limit Value - Short Term Exposure Limit) (ACGIH, 2008) is defined as a 15-minute 

### 10 TWA exposure which should not be exceeded at any time during the workday even if the 8-hour TWA is within 

### 11 the TLV-TWA. Exposures above the TLV-TWA up to the ST EL should not be longer than 15 minutes and should 

### 12 not occur more than 4 times per day. There should be at least 60 minutes between su ccessive exposures in this 

### 13 range. Value is for sodium, potassium, and calcium cyanides (as CN). 

### 14 15

e MAK (Maximale Arbeitsplatzkonzentration [Maximum Work place Concentration], Deutsche Forschungs-gemeinschaft 

### 16 [German Research Association], Germany) (DFG, 2007) is defined analogous to the ACGIH-TLV-TWA. 

### 17 18
f MAC (Maximaal Aanvaaarde Concentratie [Maximal Accepted Concentration - Peak Category]) (SDU Uitgevers 

### 19 [under the auspices of the Ministry of Social Affairs and Employment], The Hague, The Netherlands 2000) is 

### 20 defined analogous to the ACGIH-Ceiling. Value for cyanides (as CN). 

### 21 22

g OEL (Occupational Exposure Limit Values and Measures Against Air Contaminants) [Swedish Work Environment 

### 23 Authority] (AFS, 2005). Value for cyanides and hydrogen cyanide (as CN) total dust. 

### 24 25 26 27

TABLE 10. Extant Standards and Gu idelines for Potassium Cyanide

Exposure Duration Guideline 10 min 30 min 1 h 4 h 8 h AEGL-1 6.6 mg/m 3 6.6 mg/m 3 5.3 mg/m 3 3.5 mg/m 3 2.7 mg/m 3 AEGL-2 45 mg/m 3 27 mg/m 3 19 mg/m 3 9.3 mg/m 3 6.6 mg/m 3 AEGL-3 72 mg/m 3 56 mg/m 3 40 mg/m 3 23 mg/m 3 18 mg/m 3

PEL-TWA (OSHA) a 5.0 mg/m 3 (as CN) IDLH (NIOSH) b 25 mg/m 3 (as CN)
REL-TWA (NIOSH) c 5.0 mg/m 3 (as CN)[10-min]
TLV-STEL (ACGIH) d 5.0 mg/m 3 (as CN) MAK (Germany) e 5.0 mg/m 3 MAC-Peak Category (The Netherlands) f 5.0 mg/m 3 (as CN) OEL (Sweden) g 5.0 mg/m 3 (as CN)

a OSHA PEL-TWA (Occupationa l Health and Safety Administration, Permissible Exposure Limits - Time Weighted 

### 28 Average) (OSHA, 1993) is defined analogous to the ACGIH-TLV-TWA, but is for exposures of no more than 10 

### 29 hours/day, 40 hours/week. Va lue for cyanides (as CN). 

### 30 31

b IDLH (Immediately Dangerous to Life and Health, National Institute of Occupational Safety and Health) (NIOSH, 

### 32 1996) represents the maximum concentration from whic h one could escape within 30 minutes without any 

### 33 escape-impairing symptoms, or any irreversible health effects. Value for cyanides (as CN). 

### 34 35SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 16 of 38

c NIOSH REL-TWA (National Institute of Occupational Safe ty and Health, Recommended Exposure Limits - Time 

### 1 Weighted Average) (NIOSH, 2005) is defined analogous to the ACGIH-TL V-TWA. Value for cyanides except 

### 2 hydrogen cyanide. 

### 3 4

d ACGIH TLV-STEL (Threshold Limit Value - Short Term Exposure Limit) (ACGIH, 2008) is defined as a 15-minute 

### 5 TWA exposure which should not be exceeded at any time during the workday even if the 8-hour TWA is within 

### 6 the TLV-TWA. Exposures above the TLV-TWA up to the ST EL should not be longer than 15 minutes and should 

### 7 not occur more than 4 times per day. There should be at least 60 minutes between su ccessive exposures in this 

### 8 range. Value is for sodium, potassium, and calcium cyanides (as CN). 

### 9 10

e MAK (Maximale Arbeitsplatzkonzentration [Maximum Work place Concentration], Deutsche Forschungs-gemeinschaft 

### 11 [German Research Association], Germany) (DFG, 2007) is defined analogous to the ACGIH-TLV-TWA. 

### 12 13
f MAC (Maximaal Aanvaaarde Concentratie [Maximal Accepted Concentration - Peak Category]) (SDU Uitgevers 

### 14 [under the auspices of the Ministry of Social Affairs and Employment], The Hague, The Netherlands 2000) is 

### 15 defined analogous to the ACGIH-Ceiling. Value for cyanides (as CN). 

### 16 17

g OEL (Occupational Exposure Limit Values and Measures Against Air Contaminants) [Swedish Work Environment 

### 18 Authority] (AFS, 2005). Value for cyanides and hydrogen cyanide (as CN) total dust. 

### 19 20 21 22 23

TABLE 11. Extant Standards and Gu idelines for Calcium Cyanide

Exposure Duration Guideline 10 min 30 min 1 h 4 h 8 h AEGL-1 4.7 mg/m 3 4.7 mg/m 3 3.8 mg/m 3 2.4 mg/m 3 1.9 mg/m 3 AEGL-2 32 mg/m 3 19 mg/m 3 13 mg/m 3 6.6 mg/m 3 4.7 mg/m 3 AEGL-3 51 mg/m 3 39 mg/m 3 28 mg/m 3 16 mg/m 3 12 mg/m 3

PEL-TWA (OSHA) a 5.0 mg/m 3 (as CN) IDLH (NIOSH) b 25 mg/m 3 (as CN)
REL-TWA (NIOSH) c 5.0 mg/m 3 (as CN)[10-min]
TLV-STEL (ACGIH) d 5.0 mg/m 3 (as CN) MAC-Peak Category (The Netherlands) e 5.0 mg/m 3 (as CN) OEL (Sweden) f 5.0 mg/m 3 (as CN)

a OSHA PEL-TWA (Occupationa l Health and Safety Administration, Permissible Exposure Limits - Time Weighted 

### 24 Average) (OSHA, 1993) is defined analogous to the ACGIH-TLV-TWA, but is for exposures of no more than 10 

### 25 hours/day, 40 hours/week. Va lue for cyanides (as CN). 

### 26 27

b IDLH (Immediately Dangerous to Life and Health, National Institute of Occupational Safety and Health) (NIOSH, 

### 28 1996) represents the maximum concentration from whic h one could escape within 30 minutes without any 

### 29 escape-impairing symptoms, or any irreversible health effects. Value for cyanides (as CN). 

### 30 31

c NIOSH REL-TWA (National Institute of Occupational Safe ty and Health, Recommended Exposure Limits - Time 

### 32 Weighted Average) (NIOSH, 2005) is defined analogous to the ACGIH-TL V-TWA. Value for cyanides except 

### 33 hydrogen cyanide. 

### 34 35

d ACGIH TLV-STEL (Threshold Limit Value - Short Term Exposure Limit) (ACGIH, 2008) is defined as a 15-minute 

### 36 TWA exposure which should not be exceeded at any time during the workday even if the 8-hour TWA is within 

### 37SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 17 of 38

the TLV-TWA. Exposures above the TLV-TWA up to the ST EL should not be longer than 15 minutes and should 

### 1 not occur more than 4 times per day. There should be at least 60 minutes between su ccessive exposures in this 

### 2 range. Value is for sodium, potassium, and calcium cyanides (as CN). 

### 3 4

e MAC (Maximaal Aanvaaarde Concentratie [Maximal Accepted Concentration - Peak Category]) (SDU Uitgevers 

### 5 [under the auspices of the Ministry of Social Affairs and Employment], The Hague, The Netherlands 2000) is 

### 6 defined analogous to the ACGIH-Ceiling. Value for cyanides (as CN). 

### 7 8
f OEL (Occupational Exposure Limit Values and Measures Against Air Contaminants) [Swedish Work Environment 

### 9 Authority] (AFS, 2005). Value for cyanides and hydrogen cyanide (as CN) total dust. 

### 10 11 12 13 8.3. Data Adequacy and Research Needs 14 15 There are no human or animal inhalation data for sodium, potassium, or calcium cyanide. 16 However, data suggest that the cyanide moiety is responsible for the acute toxicity of these 17 compounds, and the hydrogen cyanide data set is fairly robust. 18 19SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 18 of 38



### 9. REFERENCES 1 2 3 ACGIH (American Conference of Governmental Industrial Hygienists). 2008. Threshold Limit Values and Biological 

### 4 Exposure Indices; Hydrogen cyanide and cyanide salts. American Conf erence of Governmental Industrial 

### 5 Hygienists, Inc. Cincinnati, OH. 

### 6 7 ACGIH (American Conference of Governmental Industrial Hygienists). 1996. Documentation of the Threshold Limit 

### 8 Values and Biological Exposure Indices; Hydrogen cy anide and cyanide salts. American Conference of 

### 9 Governmental Industrial Hygienists, Inc. Cincinnati, OH. 

### 10 11 AFS. 2005. Cyanides. O EL (Occupational Exposure Limit Values and Meas ures Against Air Contaminants) [Swedish 

### 12 Work Environment Authority]. 

### 13 14 ATSDR (Agency for Toxic Substances and Disease Registry). 1997. Toxicological profile for cyanide. U.S. 

### 15 Department of Health and Human Services , Public Health Service, Atlanta, GA. 

### 16 17 Cohrssen, B. 2001. Cyanides and Nitriles. In: Patty’s Toxicology fifth Edition, Volume 4. E. Bingham, B. Cohrssen, 

### 18 and C. H. Powell, Eds. John Wiley and Sons, Inc. pp. 1373-1456. 

### 19 20 DFG. 2007. Deutsche Forschungs-gemeinschaft [German Research Association. MAK (Maximale 

### 21 Arbeitsplatzkonzentration [Maximum Workplace Concentration], Germany. 

### 22 23 E.I. du Pont de Nemours and Company. 1981. Inhalation toxicity of common combustion gases. Haskell Laboratory 

### 24 Report No. 238-81. Haskell Laboratory, Newark, DE. 

### 25 26 El Ghawabi, S.H., M.A. Gaafar, A.A. El-Saharti, S.H. Ahmed, K.K. Malash and R. Fares. 1975. Chronic cyanide 

### 27 exposure: A clinical, radioisotope, and laboratory study. Brit. J. Ind. Med. 32:215-219. 

### 28 29 Grabois, B. 1954. Monthly Review 33:33; Publication of the Division of Industrial Hygiene, New York Department of 

### 30 Labor, September 1954. 

### 31 32 Hardy, H.L., W.M. Jeffries, M.M. Wasserman, and W.R. Waddell. 1950. Thiocyanate effect following industrial 

### 33 cyanide exposure - report of two cases. New Engl. J. Med. 242:968-972. 

### 34 35 HSDB (Hazardous Substances Data Bank). 2008a. Sodium Cyanide. Online data base, National Library of Medicine: 

### 36 http://toxnet.nlm.nih.gov/cgi-bin/sis

. 

### 37 38 HSDB (Hazardous Substances Data Bank). 2008b. Pota ssium Cyanide. Online data base, National Library of 

### 39
Medicine: http://toxnet.nlm.nih.gov/cgi-bin/sis

. 

### 40 41 HSDB (Hazardous Substances Data Bank). 2008c. Calcium Cyanide. Online data base, National Library of Medicine: 

### 42 http://toxnet.nlm.nih.gov/cgi-bin/sis

. 

### 43 44 IUCLID. 2000. IUCLID Dataset for potassium cyanide. European Commission- European Chemicals Bureau. 

### 45 February 18, 2000. 

### 46 47 Kirk-Othmer. 2008. Cyanides. Kirk-Oth mer Encyclopedia of Chemical Technology. 

### 48 http://www.mrw.inter science.wiley.com

. 

### 49 50 Leeser, J.E., J.A. Tomenson, and D.D. Bryson. 1990. A cross-sectional study of the health of cyanide salt production 

### 51 workers. Report No. OHS/R/2, ICI Central Toxicology Laboratory, Alderley Park, Maccles field, Cheshire, 

### 52
U.K. 

### 53 54 Maehly, A.C. and A. Swensson. 1970. Cyanide and thiocyan ate levels in blood and urin e of workers with low-grade 

### 55 exposure to cyanide. Int. Arch. Arbeitsmed. 27:195-209. 

### 56 57SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 19 of 38

NIOSH (National Institute for Occupational Safety and Health ). 1996. Documentation for Immediately Dangerous to 

### 1 Life or Health Concentrations (IDL Hs). Cyanides (as CN). U.S. Depart ment of Health and Human Services; 

### 2 U.S. Government Printing Office, Washington. (Retrieved online Nov. 2008) 

### 3 4 NIOSH (National Institute for Occupational Safety and Health). 2005. NIOSH Pocket Guide 

### 5 to Chemical Hazards. Cyanides (as CN) U.S. Departme nt of Health and Human Services; U.S. Government 

### 6 Printing Office, Washington, PB9419504 National Technical Information Service, Springfield, VA. (Retrieved 

### 7 online Nov. 2008) 

### 8 9 10 NRC (National Research Council). 2002. Acute Exposure Gu ideline Levels for Selected Airborne Chemicals. Volume 

### 11 2. Hydrogen Cyanide. pp. 211-276. 

### 12 13 Purser, D.A., P. Grimshaw, and K.R. Be rrill. 1984. Intoxication by cyanide in fires: A study in monkeys using 

### 14 polyacrylonitrile. Arch. Environ. Health 39:394-400. 

### 15 16 SDU Uitgevers. 2000. Nationale MAC List (under the auspices of the Ministry of Social Affairs and Employment), 

### 17 The Hague, The Netherlands. 

### 18 19 Smith, R.P. 1996. Toxic responses of the blood. In: Casarett & Doull's Toxicology: The Basic Science of Poisons, 5th 

### 20 Ed., McGraw-Hill, New York, pp. 350-351. 

### 21 22 Smyth, H.F., Carpenter, C.P., Weil, C.S ., Pozzani, Striegel, J.A., and Nycum, J.S. 1969. Range-finding toxicity data: 

### 23 List VII. Am. Ind. Hyg. Assoc. J. 30: 470-476. 

### 24 25SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 20 of 38



### APPENDIX A: Derivation of AEGL Values for Cyanide Salts 1 2SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 21 of 38



### 1 Derivation of AEGL-1 2 3 Derivation of AEGL-1 for Sodium Cyanide 

### 4 Key Study: Hydrogen cyanide AEGL-1 values used as target values fo r calculating the concentrations of cyanide salt needed to 

### 5 generate the hydrogen cyanide AEGL values. Calculations assume 25 degrees C and 760 mm Hg and complete hydrolysis (one mole 

### 6 of NaCN will yield one mole of HCN). 

### 7 8
10-min AEGL-1 = 2.5 ppm ÷ 1 = 2.5 ppm 

### 9 2.5 ppm x 49.0 ÷ 24.5 = 5.0 mg/m 3 

### 10 11
30-min AEGL-1 = 2.5 ppm ÷ 1 = 2.5 ppm 

### 12 2.5 ppm x 49.0 ÷ 24.5 = 5.0 mg/m 3 

### 13 14
1-hour AEGL-1 = 2.0 ppm ÷ 1 = 2.0 ppm 

### 15 2.0 ppm x 49.0 ÷ 24.5 = 4.0 mg/m 3 

### 16 17
4-hour AEGL-1 = 1.3 ppm ÷ 1 = 1.3 ppm 

### 18 1.3 ppm x 49.0 ÷ 24.5 = 2.6 mg/m 3 

### 19 20
8-hour AEGL-1 = 1.0 ppm ÷ 1 = 1.0 ppm 

### 21 1.0 ppm x 49.0 ÷ 24.5 = 2.0 mg/m 3 

### 22 23 24 Derivation of AEGL-1 for Potassium Cyanide 

### 25 Key Study: Hydrogen cyanide AEGL-1 values used as target values fo r calculating the concentrations of cyanide salt needed to 

### 26 generate the hydrogen cyanide AEGL values. Calculations assume 25 degrees C and 760 mm Hg and complete hydrolysis (one mole 

### 27 of KCN will yield one mole of HCN). 

### 28 29
10-min AEGL-1 = 2.5 ppm ÷ 1 = 2.5 ppm 

### 30 2.5 ppm x 65.1 ÷ 24.5 = 6.6 mg/m 3 

### 31 32
30-min AEGL-1 = 2.5 ppm ÷ 1 = 2.5 ppm 

### 33 2.5 ppm x 65.1 ÷ 24.5 = 6.6 mg/m 3 

### 34 35
1-hour AEGL-1 = 2.0 ppm ÷ 1 = 2.0 ppm 

### 36 2.0 ppm x 65.1 ÷ 24.5 = 5.3 mg/m 3 

### 37 38
4-hour AEGL-1 = 1.3 ppm ÷ 1 = 1.3 ppm 

### 39 1.3 ppm x 65.1 ÷ 24.5 = 3.5 mg/m 3 

### 40 41
8-hour AEGL-1 = 1.0 ppm ÷ 1 = 1.0 ppm 

### 42 1.0 ppm x 65.1 ÷ 24.5 = 2.7 mg/m 3 

### 43 44 Derivation of AEGL-1 for Calcium Cyanide 

### 45 Key Study: Hydrogen cyanide AEGL-1 values used as target values fo r calculating the concentrations of cyanide salt needed to 

### 46 generate the hydrogen cyanide AEGL values. Calculations assume 25 degrees C and 760 mm Hg and complete hydrolysis (one mole 

### 47 of Ca(CN) 2 will yield two moles of HCN). 

### 48 49
10-min AEGL-1 = 2.5 ppm ÷ 2 = 1.25 ppm 

### 50 1.25 ppm x 92.1 ÷ 24.5 = 4.7 mg/m 3 

### 51 52
30-min AEGL-1 = 2.5 ppm ÷ 2 = 1.25 ppm 

### 53 1.25 ppm x 92.1 ÷ 24.5 = 4.7 mg/m 3 

### 54 55
1-hour AEGL-1 = 2.0 ppm ÷ 2 = 1.0 ppm 

### 56 1.0 ppm x 92.1 ÷ 24.5 = 3.8 mg/m 3 

### 57 58
4-hour AEGL-1 = 1.3 ppm ÷ 2 = 0.65 ppm 

### 59 0.65 ppm x 92.1 ÷ 24.5 = 2.4 mg/m 3 

### 60 61
8-hour AEGL-1 = 1.0 ppm ÷ 2 = 0.50 ppm 

### 62 0.50 ppm x 92.1 ÷ 24.5 = 1.9 mg/m 3 

### 63 64SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 22 of 38



### Derivation of AEGL-2 1 2 Derivation of AEGL-2 for Sodium Cyanide 

### 3 Key Study: Hydrogen cyanide AEGL-2 values used as target values fo r calculating the concentrations of cyanide salt needed to 

### 4 generate the hydrogen cyanide AEGL values. Calculations assume 25 degrees C and 760 mm Hg and complete hydrolysis (one mole 

### 5 of NaCN will yield one mole of HCN). 

### 6 7
10-min AEGL-2 = 17 ppm ÷ 1 = 17 ppm 

### 8 17 ppm x 49.0 ÷ 24.5 = 34 mg/m 3 

### 9 10
30-min AEGL-2 = 10 ppm ÷ 1 = 10 ppm 

### 11 10 ppm x 49.0 ÷ 24.5 = 20 mg/m 3 

### 12 13
1-hour AEGL-2 = 7.1 ppm ÷ 1 = 7.1 ppm 

### 14 7.1 ppm x 49.0 ÷ 24.5 = 14 mg/m 3 

### 15 16
4-hour AEGL-2 = 3.5 ppm ÷ 1 = 3.5 ppm 

### 17 3.5 ppm x 49.0 ÷ 24.5 = 7.0 mg/m 3 

### 18 19
8-hour AEGL-2 = 2.5 ppm ÷ 1 = 2.5 ppm 

### 20 2.5 ppm x 49.0 ÷ 24.5 = 5.0 mg/m 3 

### 21 22 23 Derivation of AEGL-2 for Potassium Cyanide 

### 24 Key Study: Hydrogen cyanide AEGL-2 values used as target values fo r calculating the concentrations of cyanide salt needed to 

### 25 generate the hydrogen cyanide AEGL values. Calculations assume 25 degrees C and 760 mm Hg and complete hydrolysis (one mole 

### 26 of KCN will yield one mole of HCN). 

### 27 28
10-min AEGL-2 = 17 ppm ÷ 1 = 17 ppm 

### 29 17 ppm x 65.1 ÷ 24.5 = 45 mg/m 3 

### 30 31
30-min AEGL-2 = 10 ppm ÷ 1 = 10 ppm 

### 32 10 ppm x 65.1 ÷ 24.5 = 27 mg/m 3 

### 33 34
1-hour AEGL-2 = 7.1 ppm ÷ 1 = 7.1 ppm 

### 35 7.1 ppm x 65.1 ÷ 24.5 = 19 mg/m 3 

### 36 37
4-hour AEGL-2 = 3.5 ppm ÷ 1 = 3.5 ppm 

### 38 3.5 ppm x 65.1 ÷ 24.5 = 9.3 mg/m 3 

### 39 40
8-hour AEGL-2 = 2.5 ppm ÷ 1 = 2.5 ppm 

### 41 2.5 ppm x 65.1 ÷ 24.5 = 6.6 mg/m 3 

### 42 43 44 Derivation of AEGL-2 for Calcium Cyanide 

### 45 Key Study: Hydrogen cyanide AEGL-2 values used as target values fo r calculating the concentrations of cyanide salt needed to 

### 46 generate the hydrogen cyanide AEGL values. Calculations assume 25 degrees C and 760 mm Hg and complete hydrolysis (one mole 

### 47 of Ca(CN) 2 will yield two moles of HCN). 

### 48 49
10-min AEGL-2 = 17 ppm ÷ 2 = 8.5 ppm 

### 50 8.5 ppm x 92.1 ÷ 24.5 = 32 mg/m 3 

### 51 52
30-min AEGL-2 = 10 ppm ÷ 2 = 5 ppm 

### 53 5 ppm x 92.1 ÷ 24.5 = 19 mg/m 3 

### 54 55
1-hour AEGL-2 = 7.1 ppm ÷ 2 = 3.55 ppm 

### 56 3.55 ppm x 92.1 ÷ 24.5 = 13 mg/m 3 

### 57 58
4-hour AEGL-2 = 3.5 ppm ÷ 2 = 1.75 ppm 

### 59 1.75 ppm x 92.1 ÷ 24.5 = 6.6 mg/m 3 

### 60 61
8-hour AEGL-2 = 2.5 ppm ÷ 2 = 1.25 ppm 

### 62 1.25 ppm x 92.1 ÷ 24.5 = 4.7 mg/m 3 

### 63 64SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 23 of 38



### 1 Derivation of AEGL-3 2 3 Derivation of AEGL-3 for Sodium Cyanide 

### 4 Key Study: Hydrogen cyanide AEGL-3 values used as target values fo r calculating the concentrations of cyanide salt needed to 

### 5 generate the hydrogen cyanide AEGL values. Calculations assume 25 degrees C and 760 mm Hg and complete hydrolysis (one mole 

### 6 of NaCN will yield one mole of HCN). 

### 7 8
10-min AEGL-3 = 27 ppm ÷ 1 = 27 ppm 

### 9 27 ppm x 49.0 ÷ 24.5 = 54 mg/m 3 

### 10 11
30-min AEGL-3 = 21 ppm ÷ 1 = 21 ppm 

### 12 21 ppm x 49.0 ÷ 24.5 = 42 mg/m 3 

### 13 14
1-hour AEGL-3 = 15 ppm ÷ 1 = 15 ppm 

### 15 15 ppm x 49.0 ÷ 24.5 = 30 mg/m 3 

### 16 17
4-hour AEGL-3 = 8.6 ppm ÷ 1 = 8.6 ppm 

### 18 8.6 ppm x 49.0 ÷ 24.5 = 17 mg/m 3 

### 19 20
8-hour AEGL-3 = 6.6 ppm ÷ 1 = 6.6 ppm 

### 21 6.6 ppm x 49.0 ÷ 24.5 = 13 mg/m 3 

### 22 23 Derivation of AEGL-3 for Potassium Cyanide 

### 24 Key Study: Hydrogen cyanide AEGL-3 values used as target values fo r calculating the concentrations of cyanide salt needed to 

### 25 generate the hydrogen cyanide AEGL values. Calculations assume 25 degrees C and 760 mm Hg and complete hydrolysis (one mole 

### 26 of KCN will yield one mole of HCN). 

### 27 28

10-min AEGL-3 = 27 ppm ÷ 1 = 27 ppm 

### 29 27 ppm x 65.1 ÷ 24.5 = 72 mg/m 3 

### 30 31
30-min AEGL-3 = 21 ppm ÷ 1 = 21 ppm 

### 32 21 ppm x 65.1 ÷ 24.5 = 56 mg/m 3 

### 33 34
1-hour AEGL-3 = 15 ppm ÷ 1 = 15 ppm 

### 35 15 ppm x 65.1 ÷ 24.5 = 40 mg/m 3 

### 36 37
4-hour AEGL-3 = 8.6 ppm ÷ 1 = 8.6 ppm 

### 38 8.6 ppm x 65.1 ÷ 24.5 = 23 mg/m 3 

### 39 40
8-hour AEGL-3 = 6.6 ppm ÷ 1 = 6.6 ppm 

### 41 6.6 ppm x 65.1 ÷ 24.5 = 18 mg/m 3 

### 42 43 44 Derivation of AEGL-3 for Calcium Cyanide 

### 45 Key Study: Hydrogen cyanide AEGL-3 values used as target values fo r calculating the concentrations of cyanide salt needed to 

### 46 generate the hydrogen cyanide AEGL values. Calculations assume 25 degrees C and 760 mm Hg and complete hydrolysis (one mole 

### 47 of Ca(CN) 2 will yield two moles of HCN). 

### 48 49
10-min AEGL-3 = 27 ppm ÷ 2 = 13.5 ppm 

### 50 13.5 ppm x 92.1 ÷ 24.5 = 51 mg/m 3 

### 51 52
30-min AEGL-3 = 21 ppm ÷ 2 = 10.5 ppm 

### 53 10.5 ppm x 92.1 ÷ 24.5 = 39 mg/m 3 

### 54 55
1-hour AEGL-3 = 15 ppm ÷ 2 = 7.5 ppm 

### 56 7.5 ppm x 92.1 ÷ 24.5 = 28 mg/m 3 

### 57 58
4-hour AEGL-3 = 8.6 ppm ÷ 2 = 4.3 ppm 

### 59 4.3 ppm x 92.1 ÷ 24.5 = 16 mg/m 3 

### 60 61
8-hour AEGL-3 = 6.6 ppm ÷ 2 = 3.3 ppm 

### 62 3.3 ppm x 92.1 ÷ 24.5 = 12 mg/m 3 

### 63SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 24 of 38



### APPENDIX B: Time Scaling Calculation fo r Hydrogen Cyanide AEGL-1, AEGL-2, and 1 AEGL-3 2 3SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 25 of 38



### HYDROGEN CYANIDE AEGL-1 (NRC, 2002) 1 2 Key studies: El Ghawabi et al. 1975; Ha rdy et al. 1950; Grabois 1954; Maehly and 3 Swensson 1970; Leeser et al. 1990 4
5 Toxicity endpoint: No adverse e ffect in healthy adult humans o ccupationally exposed to geometric 6 mean concentration of # 1 [range 0.01-3.3 ppm, personal samplers (up 7 to 6 ppm, area samples)] or 5 ppm; mild headache in adult humans 8 occupationally exposed to 8 pp m. The exposure duration was 9 considered to be 8 hours. 10 11 Uncertainty factor: 3 for intraspecies (no sus ceptible populations were identified). The 12 uncertainty factor was applie d to the 8-hour 5 and 8 ppm 13 concentrations which resulted in co ncentrations close to the 8-hour 1 14 ppm concentration in th e Leeser et al. study. 15 16 Scaling: C 3 

### x t = k (conservative time-s caling relationship because the 17 relationship between concentrati on and exposure duration for the 18 headache effect is unknown. An 8-hour 1 ppm concentration was used 19 as the starting point for time scaling. 20 21 Calculations: (C 3 

### /uncertainty factors) x t = k 22 (1 ppm) 3 

### x 480 minutes = 480 ppm 3 

### ·minutes 23 24 25 10-minute AEGL-1 (480 ppm 3 

### ·minutes/10 minutes) 1/3 

### = 3.6 ppm 26 Because 3.6 ppm is above the highest exposure concentration in the 27 Leeser et al. (1990) study, as measured by personal monitors, the 10- 28 minute value was set equal to the 30-minute value. 29 30 30-minute AEGL-1 (480 ppm 3 

### ·minutes/30 minutes) 1/3 

### = 2.5 ppm 31 32 1-hour AEGL-1 (480 ppm 3 

### ·minutes/60 minutes) 1/3 

### = 2.0 ppm 33 34 4-hour AEGL-1 (480 ppm 3 

### ·minutes/240 minutes) 1/3 

### = 1.3 ppm 35 36 8-hour AEGL-1 1.0 ppm 37 38 39SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 26 of 38



### 1 HYDROGEN CYANIDE AEGL-2 (NRC, 2002) 2 3 Key study: Purser 1984 4
5 Toxicity endpoint: Slight cent ral nervous system depression in monkeys inhaling 60 ppm for 30 6 minutes 7 8 Scaling: C 2 

### x t = k (this document; based on regres sion analysis of incapacitation and 9 lethality data for the monkey) 10 11 Uncertainty factors: 2 for interspecies 12 3 for intraspecies 13 combined uncertainty factor of 6 14 15 Calculations: (C 2 

### /uncertainty factors) x t = k 16 (60 ppm/6) 2 

### x 30 minutes = 3000 ppm 2 

### ·minutes 17 18 19 10-minute AEGL-2 (3000 ppm 2 

### ·minutes/10 minutes) 1⁄2 

### = 17 ppm 20 21 30-minute AEGL-2 60 ppm/6 = 10 ppm 22 23 1-hour AEGL-2 (3000 ppm 2 

### ·minutes/60 minutes) 1⁄2 

### = 7.1 ppm 24 25 4-hour AEGL-2 (3000 ppm 2 

### ·minutes/240 minutes) 1⁄2 

### = 3.5 ppm 26 27 8-hour AEGL-2 (3000 ppm 2 

### ·minutes/480 minutes) 1⁄2 

### = 2.5 ppm 28 29 30SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 27 of 38



### 1 HYDROGEN CYANIDE AEGL-3 (NRC, 2002) 2 3 Key study: E.I. du Pont de Nemours 1981 4
5 Toxicity endpoint: 15-minute LC 01 

### of 138 ppm in the rat 6 30-minute LC 01 

### of 127 ppm in the rat 7 1-hour LC 01 

### of 88 ppm in the rat 8 LC 01 

### derived by probit analysis 9 10 Scaling: C 2.6 

### x t = k (this document; based on the E.I. du Pont de Nemours (1981) rat 11 data set 12 13 Uncertainty factors: 2 for interspecies 14 3 for intraspecies 15 combined uncertainty factor of 6 16 17 Calculations: (C 2.6 

### /uncertainty factors) x t = k 18 (138 ppm/6) 2.6 

### x 15 minutes = 52069.5 ppm 2.6 

### ·minutes 19 (127 ppm/6) 2.6 

### x 30 minutes = 83911 ppm 2.6 

### ·minutes 20 (88 ppm/6) 2.6 

### x 60 minutes = 64656.6 ppm 2.6 

### ·minutes 21 22 23 10-minute AEGL-3 (52069.5 ppm 2.6 

### ·minutes/10 minutes) 1/2.6 

### = 27 ppm 24 25 30-minute AEGL-3 127 ppm/6 = 21 ppm 26 27 1-hour AEGL-3 88 ppm/6 = 15 ppm 28 29 4-hour AEGL-3 (64656.6 ppm 2.6 

### ·minutes/240 minutes) 1/2.6 

### = 8.6 ppm 30 31 8-hour AEGL-3 (64656.6 ppm 2.6 

### ·minutes/480 minutes) 1/2.6 

### = 6.6 ppm 32 33 34 35SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 28 of 38



### APPENDIX C: Derivation Summary Tables for Cyanide Salts AEGLs 1 2SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 29 of 38

AEGL-1 VALUES FOR CYANIDE SALTS

10 min 30 min 1 h 4 h 8 h

Sodium Cyanide 5.0 mg/m 3 5.0 mg/m 3 4.0 mg/m 3 2.6 mg/m 3 2.0 mg/m 3

Potassium Cyanide 6.6 mg/m 3 6.6 mg/m 3 5.3 mg/m 3 3.5 mg/m 3 2.7 mg/m 3

Calcium Cyanide 4.7 mg/m 3 4.7 mg/m 3 3.8 mg/m 3 2.4 mg/m 3 1.9 mg/m 3

Key Reference: NRC (National Resear ch Council). 2002. Acute Exposure Guideline Levels for Selected Airborne Chemicals. Volume 2. Hydrogen Cyanide. pp. 211-276.
Test Species/Strain/Number:

Exposure Route/Concentrations/Durations:

Effects:

Endpoint/Concentration/Rationale: AEGL-1 values for hydrogen cyanide were used to obtain AEGL-1 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 LD 50 values) data suggest that the cyanide moiety is responsible for acute toxicity of the cyanide salts. The hydrogen cyanide AEGL-1 values were used as target values for calculating the concentrations of cyan ide salt needed to generate the hydrogen cyanide AEGL values. Calculations assume 25 degrees C and 760 mm Hg and complete hydrolysis. Uncertainty Factors/Rationale: Interspecies: Intraspecies:
Molar Adjustment Factor: 1 (Sodium cyanide and Potassium cyanide) 2 (Calcium cyanide) Animal to Human Dosimetric Adjustment:

Time Scaling:

Data adequacy: AEGL-1 values for cyanide salts were derived by analogy to HCN AEGL-1 values. The HCN database is robust.

Calcium Cyanide: The adjusted rat or al LC value for calcium cyanide is much greater (suggesting a less toxic compound) than would be expected on a molar basis for CN. However, the production of two moles of HCN was assumed per mole of calcium cyanide. This assumption will yield protective AEGL values.



### 1 2

3SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 30 of 38



### 1

AEGL-2 VALUES FOR CYANIDE SALTS

10 min 30 min 1 h 4 h 8 h

Sodium Cyanide 34 mg/m 3 20 mg/m 3 14 mg/m 3 7.0 mg/m 3 5.0 mg/m 3

Potassium Cyanide 45 mg/m 3 27 mg/m 3 19 mg/m 3 9.3 mg/m 3 6.6 mg/m 3

Calcium Cyanide 32 mg/m 3 19 mg/m 3 13 mg/m 3 6.6 mg/m 3 4.7 mg/m 3

Key Reference: NRC (National Resear ch Council). 2002. Acute Exposure Guideline Levels for Selected Airborne Chemicals. Volume 2. Hydrogen Cyanide. pp. 211-276.
Test Species/Strain/Number:

Exposure Route/Concentrations/Durations:

Effects:

Endpoint/Concentration/Rationale: AEGL-2 values for hydrogen cyanide 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 LD 50 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 cyan ide salt needed to generate the hydrogen cyanide AEGL values. Calculations assume 25 degrees C and 760 mm Hg and complete hydrolysis. Uncertainty Factors/Rationale: Interspecies: Intraspecies:
Molar Adjustment Factor: 1 (Sodium cyanide and Potassium cyanide) 2 (Calcium cyanide) Animal to Human Dosimetric Adjustment:

Time Scaling:

Data adequacy: AEGL-2 values for cyanide salts were derived by analogy to HCN AEGL-2 values. The HCN database is robust.

Calcium Cyanide: The adjusted rat or al LC value for calcium cyanide is much greater (suggesting a less toxic compound) than would be expected on a molar basis for CN. However, the production of two moles of HCN was assumed per mole of calcium cyanide. This assumption will yield protective AEGL values.



### 2SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 31 of 38



### 1

AEGL-3 VALUES FOR CYANIDE SALTS

10 min 30 min 1 h 4 h 8 h

Sodium Cyanide 54 mg/m 3 42 mg/m 3 30 mg/m 3 17 mg/m 3 13 mg/m 3

Potassium Cyanide 72 mg/m 3 56 mg/m 3 40 mg/m 3 23 mg/m 3 18 mg/m 3

Calcium Cyanide 51 mg/m 3 39 mg/m 3 28 mg/m 3 16 mg/m 3 12 mg/m 3

Key Reference: NRC (National Resear ch Council). 2002. Acute Exposure Guideline Levels for Selected Airborne Chemicals. Volume 2. Hydrogen Cyanide. pp. 211-276.
Test Species/Strain/Number:

Exposure Route/Concentrations/Durations:

Effects:

Endpoint/Concentration/Rationale: AEGL-3 values for hydrogen cyanide 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 LD 50 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 cyan ide salt needed to generate the hydrogen cyanide AEGL values. Calculations assume 25 degrees C and 760 mm Hg and complete hydrolysis. Uncertainty Factors/Rationale: Interspecies: Intraspecies:
Molar Adjustment Factor: 1 (Sodium cyanide and Potassium cyanide) 2 (Calcium cyanide) Animal to Human Dosimetric Adjustment:

Time Scaling:

Data adequacy: AEGL-3 values for cyanide salts were derived by analogy to HCN AEGL-3 values. The HCN database is robust.

Calcium Cyanide: The adjusted rat or al LC value for calcium cyanide is much greater (suggesting a less toxic compound) than would be expected on a molar basis for CN. However, the production of two moles of HCN was assumed per mole of calcium cyanide. This assumption will yield protective AEGL values.



### 2SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 32 of 38



### 1

2
APPENDIX D: Derivation Summary Tables for Hydrogen Cyanide 3

4SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 33 of 38



### 1

HYDROGEN CYANIDE AEGL-1 VALUES

10 minute 30 minute 1 hour 4 hour 8 hour

2.5 ppm

2.8 mg/m 3 2.5 ppm

2.8 mg/m 3 2.0 ppm

2.2 mg/m 3 1.3 ppm

1.4 mg/m 3 1.0 ppm

1.1 mg/m 3
Key Reference: (1) 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, Alderl ey Park, Maccles field, Cheshire, U.K. Supporting references: (2) 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. Brit. J. Ind. Med. 32:215-219. (3) Grabois, B. 1954. Monthly Review 33:33; Publication of the Division of Industrial Hygiene, New York Department of Labor, September 1954.(4) Maehly, A.C. and A. Swensson. 1970. Cyanide and thiocyanate levels in blood and urine of workers with lowgrade exposure to cyanide. Int. Arch. Arbeitsmed. 27:195-209. (5) Hardy, H.L., W.M. Jeffries, M.M. Wasserman, and W.R. Wa ddell. 1950. Thiocyanate effect following industrial cyanide exposure - report of two cases. New Engl. J. Med. 242:968-972. 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/factor ies (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 serv ice years, 16.5 (Leeser et al. 1990); Inha lation/average exposure 8 ppm/5-15 years (El Ghawabi et al. 1975); Inhalation/5 ppm/unknown/(Grabois 1954; Maehly and Swensson 1970; Hardy et al. 1950). 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 (Grabois 1954; Maehly and Swensson 1970; Hardy et al. 1950). Endpoint/Concentration/Rationale: 8 ppm from the El Ghawabi et al. (1975) study; 5 ppm from the Hardy et al. (1950),Grabois (1954), and Maehly and Swensson (1970) studies; or 1 ppm from the Leeser study, were considered noadverse-effect to mild effect concentra tions for an 8-hour work day. The NRC adjusted the chronic 8 ppm value of El Ghawabi et al. (1975) to a 1-hour exposure for healthy adults. Uncertainty Factors/Rationale: Total uncertainty factor: 3 Interspecies: Not applicable Intraspecies: 3 - 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-hour 1 ppm concentration in the Leeser et al. (1990) study. The uncertainty factor was not applied to the Leeser et al. (1990) 1 ppm concentration as it is the lowest NOAEL. Modifying Factor: Not applicable

Animal to Human Dosimetric Adjustment: Not applicable

Time Scaling: Because of the long-ter m exposure duration of the key studies, the conservative time-scaling value of n = 3 (k = 480 ppm 3 ·minutes) was applied when scaling to shorter exposure durations. The starting point for time scaling was an 8-hour concentration of 1 ppm. Data Adequacy: The preponderance of data from the key studies support an 8-hour no effect concentration of 1 ppm. The Leeser et al. (1990) stud y 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 support the safety of the derived values. The values are also supported by a NIOSH (1976) report in which 5 ppm was iden tified as a no-effect concentration in the Grabois et al. (1954) occupational study. Additional monitoring studies support the values.


### 2SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 34 of 38



### 1

HYDROGEN CYANIDE AEGL-2 VALUES

10 minute 30 minute 1 hour 4 hour 8 hour

17 ppm

19 mg/m 3 10 ppm

11 mg/m 3 7.1 ppm

7.8 mg/m 3 3.5 ppm

3.9 mg/m 3 2.5 ppm

2.8 mg/m 3
Key References: Purser, D.A. 1984. A bioassay model for testing the incapacitating effects of exposure to combustion product atmospheres using cynomolgus monkeys. J. Fire Sciences 2:20-36. Purser, D.A., P. Grimshaw and K.R. Be rrill. 1984. Intoxication by cyanide in fires: A study in monkeys using polyacrylonitrile. Arch. Environ. Health 39:393-400. Test Species/Strain/Sex/Number: Cynomolgus monkeys, 4 per exposure group (gender not stated)

Exposure Route/Concentrations/Durations: Inhalation, 60, 100, 102, 123, 147, or 156 ppm for 30 minutes

Effects: (30-minute exposures) 60 ppm: increased respiratory minute volume and slight changes in EEGs near end of exposure 100 ppm incapacitation (semi-cons cious state) in 19 minutes 102 ppm incapacitation in 16 minutes 123 ppm incapacitation in 15 minutes 147 ppm incapacitation in 8 minutes 156 ppm incapacitation in 8 minutes Endpoint/Concentration/Rationale: The 30-minute exposure to 60 ppm, a N OAEL, was chosen because the next higher tested concentration, 100 ppm, resulted in incapacitation within the 30-minute exposure period. Uncertainty Factors/Rationale: Total uncertainty factor: 6 Interspecies: 2 – The monkey is an appropriate model fo r 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 we re 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: C n x t = k where n = 2 and k = 3000 ppm 2 ·minutes based on regression analysis of timeconcentration relationships for both incapacitation times of 8 to 19 minutes and lethality data (3-60 minutes) for the monkey. Data Adequacy: Although human data are limited to primar ily occupational monitoring studies, the data base on animal studies is good. The test atmosphere in the key study was supplied via a fa ce 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. Two supporting studies were located: 1. A 30-minute 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-minute AEGL-2 of 9.2 ppm whic h 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 years reported symptoms including headache, fa tigue, effort dyspnea, and syncopes. There was no evidence that these symptoms occurred on the first day of employment.


### 2 3 4SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 35 of 38



### 1

HYDROGEN CYANIDE AEGL-3 VALUES

10 minute 30 minute 1 hour 4 hour 8 hour

27 ppm

30 mg/m 3 21 ppm

23 mg/m 3 15 ppm

17 mg/m 3 8.6 ppm

9.7 mg/m 3 6.6 ppm

7.3 mg/m 3
Key Reference: E.I. du Pont de Nemours & Co. 1981. Inhalation toxicity of common combustion gases. Haskell Laboratory Report No. 238-81. 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 minutes 110, 175, 188, 204, 230, 251, 283, or 403 ppm for 15 minutes 128, 149, 160, 183, 222, or 306 ppm for 30 minutes 76, 107, 154, 183, or 222 ppm for 60 minutes Effects (LC 01 values were calculated by Haskell Laboratory using probit analysis): 5-minute LC 01 : 283 ppm 15-minute LC 01 : 138 ppm 30-minute LC 01 : 127 ppm 60-minute LC 01 : 88 ppm

Endpoint/Concentration/Rationale: The LC 01 , the threshold for lethality, was used as the basis for the derivation of the AEGL-3. The 15-minute LC 01 was used to calculate the 10 minute value, the 30-minute LC 01 was used for the 30-minute value, and the 60-minute LC 01 was used to derive the 1-, 4- and 8-hour AEGL-3 values. Uncertainty Factors/Rationale: Total uncertainty factor: 6 Interspecies: 2 - LC 50 values for the same exposure durations for several species (rat, mouse, and rabbit) were within a factor of approximately 1.5 of each other. Base d 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: C n x t = k where n = 2.6 was derived from empirical data and used in a regression analysis of time-concentration relationships for rat LC 50 values conducted at time periods of 5, 15, 30, and 60 minutes in the key study. However, the 15-, 30-, and 60-minute va lues were calculated directly from the empirical (LC 01 ) data. The k value of 52069.5 ppm 2.6 ·minutes, based on the 15-minute LC 01 , was used for the 10-minute value and the k value of 64656.6 ppm 2.6 ·minutes, based on the 1-hour LC 01 , was used for the 4- and 8-hour 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 hours resulted in lung congestion but no deaths. Use of a total uncertainty factor of 6 and extr apolation across time to 30 minutes results in a 30-minute AEGL-3 of 22 ppm which is similar to the derived value of 21 ppm.SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 36 of 38



### APPENDIX E: Category Plots for Cyanide Salts 1 2SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 37 of 38



### 1 2 3 4
5

1 10 100mg/m3

0 60 120 180 240 300 360 420 480 min Human - No E f

Human - Disc o

Human - Disa b

A nimal - No E f

A nimal - Disc o

A nimal - Disa b

A nimal - Parti a

A nimal - Leth a

AEGL 

### Sodium Cyanide AEGLs

AEGL-3

AEGL-1 AEGL-2



### 6SELECTED CYANIDE SALTS Propose d: 04-2009/ Page 38 of 38

1 10 100mg/m3

0 60 120 180 240 300 360 420 480 min Human - No E f

Human - Disc o

Human - Disa b

A nimal - No E f

A nimal - Disc o

A nimal - Disa b

A nimal - Parti a

A nimal - Leth a

AEGL 

### Potassium Cyanide AEGLs

AEGL-3

AEGL-1 AEGL-2



### 1

1 10 100mg/m3

0 60 120 180 240 300 360 420 480 min Human - No E f

Human - Disc o

Human - Disa b

A nimal - No E f

A nimal - Disc o

A nimal - Disa b

A nimal - Parti a

A nimal - Leth a

AEGL 

### Calcium Cyanide AEGLs

AEGL-3

AEGL-1 AEGL-2



### 2