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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
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:
While this is not a guideline study, these data are generated by one of the premier experts in the toxicology of cyanides, Dr. Brian Ballantyne, author of "Clinical and Experimental Toxicology of Cyanides", 1987. This data was reviewed by and found to be valid by the ECETOC Task Force on Cyanides, who authored the ECETOC JACC No. 53 report.

Data source

Reference
Reference Type:
publication
Title:
Acute percutaneous systemic toxicity of cyanides
Author:
Ballantyne B.
Year:
1994
Bibliographic source:
J Toxicol – Cut and Ocular Toxicol 13:249-262.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Animals were exposed to a solution of cyanide via a specially-designed application vessel attached to the shaved and depilitated skin, intact and abraded. Observations were made of clinical signs and death, and time to these signs was noted.
GLP compliance:
not specified
Test type:
other:
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
97% pure

Test animals

Species:
rabbit
Strain:
not specified
Sex:
female

Administration / exposure

Type of coverage:
other: specially-designed phalanges for attachment of vessel containing HCN
Details on dermal exposure:
Exposed skin was depilitated, and a glass application vessel was attached using double-sided adhesive EEG electrode disks, cut in the middle to allow direct exposure. Solutions of cyanide were instilled into the well of the application chamber using a calibrated pipette, after which it was seals. A volume of 0.1 ml/kg was used. Animals were slightly restrained during the exposure, after which the cylinders were removed and the chambers washed out.
Duration of exposure:
up to 6 hours
No. of animals per sex per dose:
9-10
Control animals:
not specified
Details on study design:
The skin of some rabbits was abraded; the remaining rabbits' skin was intact.
Statistics:
95% Confidence Limits calculated

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 11.28 mg/kg bw
95% CL:
> 9.17 - < 12.67
Remarks on result:
other: NaCN solution on abraded skin
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 14.63 mg/kg bw
95% CL:
> 13.75 - < 15.35
Remarks on result:
other: NaCN solution on intact skin
Sex:
female
Dose descriptor:
LD50
Effect level:
7.35 mg/kg bw
Based on:
test mat.
95% CL:
6.68 - 7.81
Remarks on result:
other: Dry NaCN powder on abraded skin
Sex:
female
Dose descriptor:
LD50
Effect level:
11.83 mg/kg bw
Based on:
test mat.
95% CL:
7.4 - 18.92
Remarks on result:
other: NaCN powder on moistened intact skin
Sex:
female
Dose descriptor:
LD50
Effect level:
> 200 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Dry NaCN powder on intact skin
Mortality:
50%
Clinical signs:
no data
Body weight:
no data
Gross pathology:
no data
Other findings:
no data

Any other information on results incl. tables

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 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

Interpretation of results:
Toxicity Category I
Remarks:
Migrated information as per Regulation(EC) No. 1272/2008. Criteria used for interpretation of results: EU
Conclusions:
The LD50 of a NaCN solution by the dermal route to rabbits with intact skin was 14.63 mg/kg bw. The LD50 in rabbits with abraded skin was 11.28 mg/kg bw. These correspond to 0.231 and 0.299 mmol NaCN/kg, respectively. Dry powder NaCN was also tested on intact and abraded skin. The LD50 of the powder on intact moistened skin was 11.83 mg/kg, while it was over 200 mg/kg when the skin remained dry. In abraded skin, the LD50 of dry powder was 7.35 mg/kg. The onset of symptoms was rapid, within minutes.
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.