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Toxicological information

Direct observations: clinical cases, poisoning incidents and other

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Administrative data

Endpoint:
direct observations: clinical cases, poisoning incidents and other
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
A review of experimental data on cyanides was undertaken by an ECETOC Task Force, and published as 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)”. The report is a weight of evidence approach to an extensive body of literature by this scientific non-governmental organization (NGO). This group evaluated this study and judged the methods and results to be valid and consistent with other data.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
review article or handbook
Title:
Unnamed
Year:
2007

Materials and methods

Study type:
other: Literature review
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Comprehensive literature review and recalculation/integration of data by the ECETOC Task Force on Cyanides.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Subjects:
various species of animals, including goats and monkeys.
Route of exposure:
inhalation
Reason of exposure:
intentional
Details on exposure:
See Barcroft, 1931, for methods. Animals were exposed in a free-standing chamber with an air-lock at the entrance.

Results and discussion

Clinical signs:
A four hour LD50 value for humans is estimated to be 103 mg/m3. The LD01 is estimated to be 45 mg/m3.
Outcome of incidence:
determination of LD50 value

Any other information on results incl. tables

The work of Barcroft (1931) and McNamara (1976) indicate that the sensitivity of humans is comparable to that of monkeys and goats. On this basis, the ECETOC Task Force combined the observations on goats and monkeys into one group. The LC50 and the LC01 values of this combined group were estimated, for a 4 hour exposure, to be 103 mg/m3 and 45 mg/m3, respectively. These values are believed be a good estimate of the sensitivity of the acute inhalation toxicity of HCN to humans. The LC50 estimates fit well with accidental and intentional exposure, as reported elsewhere.

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.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.

Applicant's summary and conclusion

Conclusions:
The ECETOC Task Force on Cyanides reviewed literature on acute inhalation toxicity of cyanides among various species, with the aim of estimating the LD50 for humans. The major data source is a 1931 study by Barcroft, which, though dated, provides information amenable to extrapolation to humans. A four hour LD50 value for humans is estimated to be 103 mg/m3. The LD01 is estimated to be 45 mg/m3.
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.