Sodium cyanide

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Additional information

Potassium cyanide and sodium cyanide can be considered as a chemical category, along with hydrogen cyanide (HCN) and acetone cyanohydrin (ACH, also known as 2-hydroxy-2-methylpropanenitrile), based on structural similarity, similar physico-chemical properties and common breakdown/metabolic products in physical and biological systems. Particular attention is paid to the dissociation constant of HCN. In the vast majority of environmental and physiologic conditions, the cyanide salts will dissolve in water to form hydrogen cyanide. The physico-chemical hazards and toxicity result from the activity of this common proximal toxicant, HCN. Support for this category approach is provided in examination of acute and chronic toxicity by oral, dermal, ocular and intraperitoneal administration of various forms of cyanide and in aquatic and terrestrial compartments of the environment, which provide consistent and comparable values when expressed as mmol/kg bw.  An ECETOC Task Force, in the 2007 ECETOC Joint Assessment of Commodity Chemicals ( JACC ) Report No. 53, “Cyanides of Hydrogen, Sodium and Potassium, and Acetone Cyanohydrin (CAS No. 74-90-8, 143-33-9, 151-50-8 and 75-86-5)” supports the development of this chemical category. Hydrogen cyanide (Index No.006-006-00-X) and salts of hydrogen cyanides (Index No.006-007-00-5) are both listed in Annex VI,Table 3.1 of Regulation (EC) No. 1272/2008, entry 006-007-00-5, and are restricted in comparable ways taking into account physical characteristics. Thus, the assignment of potassium cyanide and sodium cyanide to a chemical category does not result in a less protective regulatory status.

Fertility effects of cyanides are available in several subchronic toxicity protocols. An oral 13-week guideline study of KCN in drinking water was undertaken in male CD rats at doses of 40, 80 and 140 mg/kg bw/day for 13 weeks. These doses are the highest administered to rats in similar studies. An extra control group was included: a “paired-drinking” group consuming only the lowest amount of water imbibed by the high dose treated group.  No overt toxicity was noted, and major findings were significant changes in food consumption, water consumption, body weight changes and relative organ weights. The paired-drinking group was informative in that most of the changes observed in the high dose group were also observed in this group, indicating that the effects were due to water restriction rather than to cyanide. The absolute weight of the testes indicated a slight tendency to decrease in the medium dose group, and was significantly reduced in the high dose group. No histopathology was observed in the testes.  The NOAEL for reproductive effects was the mid-dose group receiving 80 mg KCN/kg bw/d, equivalent to 32 mg CN ion/kg bw/d (Leuschner, 1989), while the NOAEL for general systemic toxicity (diminished weight gain) was 40 mg/kg bw/d.

The Hebert (1993) study discusses possible effects of sodium cyanide on male reproductive parameters. These effects were noted by the authors to be minor having little biological significance. The decreased caudal epididymal weights and decreased sperm mobility, along with decreased urine volume and increased urine specific gravity, are likely effects resulting from decreased water consumption, dehydration and stress. 

Guideline reproductive toxicity and developmental toxicity studies were undertaken by Monsanto using inhalation exposure to ACH. These indicated no evidence of fertility or teratogenic effects. Sousa, et.al, 2007, in Wistar rats, demonstrated no teratogenic effects of KCN.

A NOAEL of 100 ppm (8.6 and 9.6 mg CN‾/kgbw/d) in male and female mice can be derived from the drinking-water study of Hébert (1993). This is consistent with the NOAEL of 8.2 mg HCN /kgbw/d (7.9 mg CN‾/kgbw/d) in rats from the fumigated diet study conducted by Howard and Hanzal (1955) and lower than the Leuschner data (1989). This value is also essentially the same as the NOEL of 57.2 and 58.6 ppm ACH (8.4 and 8.6 mg CNˉ/kgbw) for reproductive effects in male and female rats, respectively, obtained from the inhalation studies of Monsanto (1985). It provides some confidence that the slight effects observed by Hébert in male rats were unlikely to be cyanide related. More likely, these were effects secondary to administration of cyanide in drinking water (decreased water consumption, dehydration, stress).

Short description of key information:
Under physiological conditions, cyanide salts form HCN. The NOAELs for CN- from fertility and developmental toxicity studies are higher than the NOAELs for maternal toxicity. Cyanides are overtly toxic to the reproductive organs, but there is no reason to conclude that this system is any more sensitive than other organ systems. The reproductive system is not a specific target for cyanide toxicity.

Effects on developmental toxicity

Additional information

In a teratogenicity study, pregnant Sprague-Dawley rats (25/group) were dosed on days 6 to 15 of gestation with 0, 1, 3 or 10 mg ACH/kgbw (corresponding to 0, 0.31, 0.92 and 3.06 mg CNˉ/kgbw). Dose selection was made on the basis of marked maternal toxicity observed at higher doses observed in a range-finding study (Monsanto, 1983). No deaths were observed during the exposure period. Maternal toxicity was evident by slight reductions in body-weight gain in mid and high exposure groups. Statistically significant differences between the high-dose group and controls were observed for the number (per dam) of corpora lutea and number of implantations. Numbers (per dam) of viable foetuses, post-implantation losses, mean foetal body weight and foetal sex distribution at all doses were comparable to controls. The incidence of foetal malformations and developmental variations for all foetuses of treated rats were also comparable to controls (Monsanto, 1983). It may be concluded that 3 mg CNˉ/kgbw was not teratogenic in the rat in the presence of maternal toxicity.

Sousa investigated the developmental effects in Wistar rats of oral potassium cyanide at doses up to 30 mg/kg bw/d (12 mg CN-/kg bw/d). There were no teratogenic effects seen in offspring. While some histopathologic effects were noted in several organs in animals of both generations, the severity was significantly lower in the offspring. The evidence suggests that the adult dams have a higher sensitivity to cyanide than do the developing foetuses.

These data indicate that there is no increased risk for reproductive toxicity of cyanides at concentrations which are not systemically toxic to adults.

Justification for classification or non-classification

The results of reproductive toxicity studies indicate that cyanide compounds are not teratogens or reproductive toxicants.