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Description of key information

Sodium or potassium cyanide is an alkali salt of the anion, cyanide, CN-, which is the solitary functional group which defines its chemical and toxicologic activity.  These salts are soluble in water, resulting in the immediate formation of HCN, as the pKa value (dissociation constant) is  9.36 at 20°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.  A two-year assay of rats given feed impregnated with HCN resulted in no increased incidence or burden of tumors.

Key value for chemical safety assessment

Justification for classification or non-classification

There is insufficient evidence from chronic and subchronic animal studies, and from genetic testing and human surveys, to support classification of cyanide salts as carcinogens.

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.

In a limited 2-year study in rats receiving diets fumigated with HCN, a NOAEL of approximately 8.2 mg/kgbw/d (7.9 mg CN‾/kgbw/d) was identified. The study was performed with the maximum tolerated dose level determined in a preliminary study. No treatment-related effects were observed and there was no increase in tumour incidence compared to untreated controls (Howard and Hanzal, 1955). The results of this study are in accordance with the 90-day repeated-dose studies and indicate that the NOAEL is probably not decreasing with increasing exposure time. This is consistent with the mode of action relating to steady-state tolerated levels of cyanide and thiocyanate.

With regard to carcinogenicity there is no concern for this endpoint from genotoxicity studies.

The only possibility of a non-genotoxic tumorigenic effect could be related to the main metabolite, thiocyanate and its effect on the thyroid. Permanent stimulation of the thyroid in the case of a chronically elevated serum thiocyanate level, in particular when in combination with iodine deficiency, could theoretically also lead to a formation of thyroid tumours. Competitive inhibition of iodine uptake into the thyroid by thiocyanate leads to a reduced formation of thyroid hormones (T3 and T4). This triggers, via a negative feed-back mechanism, the production of TRH that, in turn, induces production of TSH. If the TSH level is chronically elevated, thyroid cell hypertrophy and hyperplasia may result. This may ultimately lead to some potential for neoplasia. Under conditions where thyroid-pituitary homeostasis is maintained, the steps leading to possible tumour formation are not expected to develop and the chances of tumour formation are negligible. If exposure to levels leading to goitre formation is avoided, there should also be no risk of tumour formation.  Furthermore, in the epidemiological studies in areas with endemic goitre and cretinism, no increase in thyroid tumour formation was observed. This indicates that the risk of neoplasia in exposed humans is not significant.

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