Hydrogen cyanide

Endpoint summary

Description of key information

LC50 and LC01 values have been estimated for human exposure, based on the duration of time during which inhalation occurs. These values are derived from acute studies in large animals. LC50 values range from 676 mg/m3  for 5 minutes, to 73 mg/m3  for 480 minutes. LC01 values range from 296 mg/m3 for 5 minutes,  to 32 mg/m3 for 480 minutes.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

3.62 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

103 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2.34 mg/kg bw

Additional information

HCN is a very toxic substance by oral, dermal, inhalation or ocular routes in rats, mice and rabbits. The lowest LD50 (mg/kgbw) for HCN in rats is 3.62, and for rabbits in 2.49. The dermal toxicity of a solution of HCN was 2.34 mg/kgbw in abraded skin of rabbits. The inhalation LC50 in humans is estimated to 103 mg/m³. This is supported by 1 hour values for inhalation toxicity for free-moving rats of 144 mg/m³ (162 ppm) and 6 hour values of 68 mg/m³. The LD50 for HCN after intraocular instillation is 1.04 mg/kgbw in rabbits.

Cyanides are known to be respiratory poisons (the cyanide anion reversibly binds to the ferric ion of the enzyme cytochrome c oxidase (also known as aa₃), preventing transport of electrons from cytochrome c oxidase to oxygen.) As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy.) Consequently, tissues that depend highly on aerobic respiration, such as the central nervous system and the heart, are particularly sensitive to cyanide.

Justification for selection of acute toxicity – oral endpoint
valid scientific study

Justification for selection of acute toxicity – inhalation endpoint
valid scientific study; LC50 is for human exposure

Justification for classification or non-classification

Hydrogen cyanide is categorized at Category 1 for acute oral, dermal, inhalatory and intraocular toxicity, according to Regulation EC No. 1272/2008. The acute oral, dermal and intraocular LD50’s are less than 5 mg/kgbw. The acute inhalatory LC50 in humans is estimated to be 103 mg/m³ for 4 hours.

The available data do not support hydrogen cyanide being classified for STOT-SE. UNECE, in its GHS revision 4 guidance, and ECHA, in its Guidance on the Application of the CLP Criteria (Section 3.8.1, 2012 and 2015), clearly state that designation as STOT in intended to address all significant nonlethal health effects not specifically addressed by other GHS classifications. Cyanides are classified as highly toxic (Category 1) under the GHS system with the Skull and Crossbones pictogram and the signal word “Danger”. Cyanides are known respiratory poisons and the symptoms of poisoning observed in single dose studies in animals, and from accidental exposures in humans, are consistent in pointing to the high oxygen demand organs like the brain and heart as being most sensitive. However, as these effects lead to lethality at concentrations relevant to the classification of cyanide for acute toxicity, the existing classification under GHS as acutely toxic would take precedence and assignment of STOT-SE to these organs would be duplicative and inappropriate. The classification as acutely toxic is considered sufficient to communicate the toxicological effect(s) adequately.