Registration Dossier

Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Experimental data was reviewed by the ECETOC Task Force, author of the 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)”, 2007. The report is a weight of evidence approach to an extensive body of literature, much of which was undertaken prior to development of guidelines. The report was peer reviewed by the scientific non-governmental organization (NGO), which judged the data to be reliable with restrictions.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
review article or handbook
Title:
Artifacts in the definition of toxicity by cyanides and cyanogens.
Author:
Ballantyne B.
Year:
1983
Bibliographic source:
Fundam Appl Toxicol 3:400-408

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Intraocular instillation in rabbits
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
not specified
Sex:
female

Administration / exposure

Route of administration:
other: intraocular
Vehicle:
water
Details on exposure:
Instillation volume is 0.03 ml.
Statistics:
95% Confidence Limits calculated.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 1.04 mg/kg bw
95% CL:
> 0.96 - < 1.13
Mortality:
50%
Clinical signs:
Rapid breathing, weak and ataxic movements, convulsions, tonic spasms, irregular and shallow breathing, coma, cessation of breathing
Other findings:
Eye irritation develops, with mild chemosis and conjunctival hyperaemia which facilitates absorption. In surviving animals, the conjunctival effects become more marked and, by 24 hours, diffuse corneal opacification develops. These effects subside slowly, but mild conjunctivitis and keratosis are still present at 7 days post-instillation.

Any other information on results incl. tables

Time to onset of signs ranged from 30 to 60 seconds, and times to convulsions from 45 to 90 seconds. Time to death was 3 minutes.

There is no "first-pass" effect of metabolism with this route of administration.

Applicant's summary and conclusion

Conclusions:
The LD50 for intraocular instillation of HCN to rabbits is 1.04 mg/kg bw, with rapid onset of death, within minutes.