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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
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.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
review article or handbook
Title:
Toxicology of Cyanides
Author:
Ballantyne B
Year:
1987
Bibliographic source:
Clinical and Experimental Toxicology of Cyanides, (Ballantyne B and Marrs TC, ed), IOP Publishing, Wright, Bristol, UK, pp. 41-126.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Deviations:
not specified
Remarks:
no information given on details of methods
Principles of method if other than guideline:
A reputable corporate laboratory (Union Carbide, Danbury, CT, U.S.A., by Dr. Bryan Ballantyne, MD) generated data on lethal doses to animals, which was judged by the ECETOC Task Force to be valid.
GLP compliance:
not specified
Test type:
other: method is valid as judged by ECETOC Task Force
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
KCN

Test animals

Species:
rat
Strain:
not specified
Sex:
female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Details on study design:
no data
Statistics:
95% Confidence Limits were calculated for the LD50.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 7.49 mg/kg bw
95% CL:
> 6.68 - < 8.48
Remarks on result:
other: This is one of 8 LD50 studies in rats which were dosed with either HCN, NaCN, KCN or Acetone Cyanohydrin (ACH). The results of all studies indicated a LD50 of < 10.0 mg/kg bw.
Mortality:
50% of treated animals
Clinical signs:
The major target site for cyanide, where there is induction of a potentially lethal cytotoxic hypoxia, is the brain. A dose-dependent suppression of electroencephalographic activity has been observed. While large doses of cyanide produce permanent EEG silence, a reversible effect can be achieved with careful cyanide titration. Various central neuropathological features have been described in animals and, to a lesser extent, in humans following sublethal and potentially lethal doses of cyanides.

There is also evidence suggesting that the heart is an important target in the expression of severe sublethal and lethal toxicity from cyanide. During cyanide poisoning, the concentrations of cyanide are consistently high in the myocardium, irrespective of species and route of exposure. Cardiac failure is a prime factor in the acute toxicity of cyanide.

Cyanide produces increased cerebral blood flow in various species and has marked effects on general systemic blood pressure. Aortic receptor studies suggest that cyanide does not act by miscarinic, H2-histamingeric, serotonergic or alpha-adrenergic mechanisms. If cyanide has an effect on coronary arteries similar to that on the aorta, hypoxia-induced depolarization can enhance cyanide-induced coronary artery vasoconstriction, hastening myocardial ischaemia.

Any other information on results incl. tables

The LD50 of KCN in female rats is 7.49 mg/kg bw. This corresponds to 0.115 mmol/kg bw.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category II
Remarks:
Migrated information 5 < LD50 <50 Criteria used for interpretation of results: EU
Conclusions:
The literature on acute oral toxicity in animals was reviewed by the ECETOC Task Force.  The lowest oral LD50 for rats is 7.49 (mg/kgbw) . Target organs include brain, heart and vascular tissue.
Executive summary:

KCN is a highly toxic compound by the oral route in rats, and is classified according to Table 3.1 of Regulation EC No. 1272/2008 (Acute Toxicity Hazard Category 2). The lowest oral LD50 for KCN reported for rats is 7.49. mg/kg body weight.