Hydrogen cyanide

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

12.5 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on fertility: via inhalation route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

1 mg/m³

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Reproductive toxicity studies of acetone cyanohydrin, sodium cyanide and potassium cyanide are all informative toward understanding the reproductive effects of hydrogen cyanide. Regardless of whether the exposure is to gaseous HCN or ACH, or via a soluble cyanide salt, it is HCN which is absorbed into the blood after oral, dermal or inhalation exposure. The form of cyanide to which exposure takes place, i.e. a simple salt or the free acid, does not influence the distribution, metabolism or excretion from the body. 

 

There is limited information available from the report of a 13-week subchronic study of NaCN in the drinking water of F344 rats and B6C3F1 mice at doses of up to 12.5 and 26.5 mg CN ion/kg bw/d, respectively (Hebert, 1993). While minor effects were seen in cauda epididymal weight, sperm motility and sperm head counts, the effects are likely related to water restriction, dehydration and resultant stress.  Water restriction was also observed in a 13-week subchronic study of KCN in CD rats at significantly higher doses (up to 160 mg KCN/kg bw/day).  An additional control group of animals which received equivalent amounts of water as the high dose KCN group demonstrated comparable decreases in body and organ weights (including testes), indicating that cyanide was not the causative agent in the organ weight changes.

There are two fertility studies with acetone cyanohydrin (ACH), one for male and one for female fertility. There were no effects on fertility observed when ACH was given by inhalation up to concentrations, limited by the threshold of acute lethality, to male or female rats. In a teratology study of ACH in rats, there were no differences in the incidence of foetal malformations and developmental variations between foetuses of treated rats and controls. Subchronic studies of sodium cyanide or potassium cyanide which have suggested minor effects on male reproduction have been confounded by fluid restriction and stress, as evidenced by similar findings in controls provided comparable water supplies.

 

Justification for selection of Effect on fertility via oral route:
valid scientific study

Effects on developmental toxicity

Description of key information

A standard teratology protocol was used in an oral study of Acetone cyanohydrin at concentrations of 0, 1, 3 and 10 mg/kg bw/day .    The incidence of fetal malformations and developmental variations was comparable between test and control groups.   Acetone cyanohydrin did not elicit a teratogenic response when administered by the oral route to Charles River rats at  10 mg/kg/day. 

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

10 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

The only studies that give a clear indication of the relative sensitivity of the reproductive system are those that have used ACH. ACH showed no evidence of teratogenic effects following gavage dosing in rats up to and including doses that produced maternal toxicity.

Justification for classification or non-classification

Hydrogen cyanide is not specifically toxic to the reproductive system or to developing organisms.