Registration Dossier

Administrative data

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study acceptable for assessment, basic data given

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991

Materials and methods

Principles of method if other than guideline:
Modification of Burton et al (1981), Food and Cosmetic Toxicology, vol. 19, pgs 471-480. This technique ranks materials of known ocular irritation in vivo against % corneal swelling of isolated eyes. A threshold value has been established at 15 % above which a material is considered to cause severe
effects when tested in vivo.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals / tissue source

Species:
rabbit
Strain:
not specified

Test system

Vehicle:
unchanged (no vehicle)
Duration of treatment / exposure:
10 seconds
Observation period (in vivo):
0.5 h, 1.0 h, 2.0 h, 3.0 h, 4.0 h, 5.0 h
Number of animals or in vitro replicates:
two isolated rabbit eyes

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
other: Mean % Corneal Swelling
Basis:
mean
Time point:
other: 0.5 h
Score:
6.85
Remarks on result:
other: +/- S.DEV 0.66
Irritation parameter:
other: Mean % Corneal Swelling
Basis:
mean
Time point:
other: 1.0 h
Score:
12.64
Remarks on result:
other: +/- S.DEV 2.82
Irritation parameter:
other: Mean % Corneal Swelling
Basis:
mean
Time point:
other: 2.0 h
Score:
15.98
Remarks on result:
other: +/- S.DEV 1.54; threshold value of 15 % exceeded
Irritation parameter:
other: Mean % Corneal Swelling
Basis:
mean
Time point:
other: 3.0
Score:
15.98
Remarks on result:
other: +/- S.DEV 1.54; threshold value of 15 % exceeded
Irritation parameter:
other: Mean % Corneal Swelling
Basis:
mean
Time point:
other: 4.0 h
Score:
21.62
Remarks on result:
other: +/- S.DEV 0.47; threshold value of 15 % exceeded
Irritation parameter:
other: Mean % Corneal Swelling
Basis:
mean
Time point:
other: 5.0 h
Score:
21.62
Remarks on result:
other: +/- S.DEV 0.47; threshold value of 15 % exceeded

Applicant's summary and conclusion

Interpretation of results:
other: severely ocular irritant
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The TS caused significant corneal swelling to two isolated rabbit eyes after an exposure time of 10 seconds.
The threshold value of 15 % was exceeded after 2 hours. The entire observation time was up five hours.

Although the design of this study does not apply to an established in vitro method and only a very short summary is available instead of a complete report, the study may be regarded as valid with restrictions (Klimisch 2, basic data given) and used for assessment if 4,6-dichloropyrimidine is classified as Xi; R41 (risk ofserious damage to eyes) for precautionary reasons. Regarding the severity of the response obtained in isolated eyes an in vivo study should not be performed due to animal welfare.