Registration Dossier

Administrative data

Description of key information

Potassium cyanide is an alkali salt of the anion, cyanide, CN-, which is the solitary functional group which defines its chemical and toxicologic activity.  The salt is soluble in water, resulting in the immediate formation of HCN, as the pKa value (dissociation constant) is  9.11 at 30°C.  At the physiological pH of about 7, cyanide salts are distributed in the body as HCN and are not present as either the salt or the free CN‾ ion.  Data are availabe for the estimation of dose descriptors and DNELs in humans, thus avoiding extrapolation from animal species.  Calculations on LD50 values from animal studies provide comparable values for DNELs.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
7.49 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
103 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
14.29 mg/kg bw

Additional information

Cyanides are very toxic by the oral, dermal, inhalation or ocular routes in rats, mice and rabbits. The lowest LD50 (mg/kg bw) for HCN in rats is 3.62, and for rabbits is 2.49. The dermal LD50 of a solution of HCN was 2.34 mg/kg bw in abraded skin of rabbits. For KCN specifically, the oral LD50 is 7.49 mg/kg bw, and the dermal LD50 in abraded skin is 14.29 mg/kg bw. Although there are no guideline studies available for inhalation for 4 hours duration, the ECETOC Task Force on Cyanides extrapolated the inhalatory LC50 for a 4 hour exposure to HCN (CN-) for rats to be 103 mg/m3.

Dugard (1984) determined that a 70 kg person could absorb 30 mg CN-/hour through the skin before experiencing toxicity.

The ECETOC Task Force generated an estimate of a human LC01, a value where 1% of an occupationally exposed population would experience a death from cyanide vapor. This is essentially a No Effect Level. For inhalation exposures, this is dependent upon the length of time of the exposure. The LC01 value for a 5 minute exposure is 296 mg HCN/m3, for 15 minutes is 173 mg HCN/m3 and for 60 minutes is 88 mg HCN/m3.

The onset of cyanide toxicity is normally very rapid (within seconds to minutes) in particular via the inhalation and oral routes. Early symptoms of cyanide intoxication include headache, vertigo and dyspnoea followed by coma and convulsions, and finally respiratory arrest, cardiovascular collapse and death..

The ECETOC Task Force on Cyanides (2007) developed interspecies scaling and extrapolation data to estimate that the LC50 for humans for a 4 h exposure is 103 mg/m3, and the LC01 for humans for a 4 h exposure is 45 mg/m3. The 15-minute LC01 in humans is estimated to be 173 mg/m3.

Based on experience in human cases involving intentional suicide or inadvertant occupational exposure, data are available to estimate NOAEL values or dose descriptors for humans. Rieders (1971) found that 200 mg of inorganic cyanide salt was the minimal lethal dose for oral exposure. For dermal exposure, 100 mg of inorganic salt was the minimal lethal dose, although this exposure was much slower. Cyanide salts, when hydrated on the surface of the skin, form HCN which moves through skin 30 times faster than the salt (Dugard, 1987). The Scientific Committee on Occupational Exposure Levels (SCOEL, 2005) recommended a short-term exposure limit of 5 mg CN-/m3 from HCN, NaCN and KCN. Taking into account molar conversion, a value of the inhalation limit for KCN is 12.5 mg/m3.

 

Justification for classification or non-classification

The acute oral and dermal LD50's for cyanide salts are less than 5 mg/kg bw. The acute inhalatory 4-h LD50 for HCN in rats is estimated to range between 68-103 mg/m3. Cyanide compounds are tightly regulated, due to their high acute toxicity. Classification and labeling is dictated through listing in Regulation (EC) No. 1272/2008, Nos 006-006-00-X and 009-007-00-5, indicating Acute Category 2 for oral toxicity, Acute Category 1 for dermal toxicity, and Acute Category 2 for inhalation toxicity.  However, as the values for acute oral toxicity and acute inhalation toxicity are close to the threshold for the more toxic category, all acute toxicity classes are set to Category 1. Both the oral and inhalation routes of exposure carry a skin notation.