Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test performed before GLP guideline implementation. Important aspects (dosing, observation times, grading criteria) comparable with current OECD guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Federal Register 38, No. 187, 27.9.1973, p 27019
Deviations:
no
GLP compliance:
no
Remarks:
previous to GLP implementation

Test material

Constituent 1
Chemical structure
Reference substance name:
4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid
EC Number:
201-901-3
Cas Number:
89-36-1
Molecular formula:
C10H10N2O4S
IUPAC Name:
4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source:Hoechst AG, breeding colony
- Weight at study initiation: 2.5 - 3.4 kg
- Housing: single caged
- Diet: standard diet ERKA Z-6000 ad lilbitum
- Water: ad libitum

Test system

Vehicle:
physiological saline
Controls:
other: one eye, remaining untreated, serves as a control
Amount / concentration applied:
- Amount(s) applied (volume or weight with unit): 100 mg
- Concentration (if solution): moistened with 0.05 mL physiological saline
Duration of treatment / exposure:
Rinsing with physiol. saline: 24 h after instillation
Observation period (in vivo):
examinations at 1, 7, 24, 48 and 72 h after instillation
Number of animals or in vitro replicates:
6
Details on study design:
100 mg of the test material, moistened with physiological saline, is placed in one eye of each animal by gently pulling the lower lid away from the eyeball to form a cup into which the test substance is dropped. The lids are then gently held together for one second and the animal is released. The other eye, remaining untreated, serves as a control. 24 h after instillation the eyes were rinsed with physiological saline. The eyes are examined and the grade of ocular reaction is recorded at 1, 7, 24, 48, and 72 hours after instillation. After the recording of observations at 24 hours, eyes were further examined after applying fluorescein.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: # 2-4, 6 each
Time point:
other: mean of 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: grade 1 and 2 cornea opacity were observed 1 and 7 h after instilliation, which were fully reversible after 24 h
Remarks on result:
other: 4 animals
Irritation parameter:
cornea opacity score
Basis:
animal: # 1, 5 each
Time point:
other: mean of 24, 48 and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: 2 animals
Irritation parameter:
iris score
Basis:
animal: # 2, 4-6 each
Time point:
other: mean of 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: grade 1 (iris) was observed 1 and 7 h after instilliation, which was fully reversible after 24 h
Remarks on result:
other: 4 animals
Irritation parameter:
iris score
Basis:
animal: # 1, 3 each
Time point:
other: mean of 24, 48 and 72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: 2 animals
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean of 24, 48 and 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean of 24, 48 and 72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean of 24, 48 and 72 h
Score:
1.3
Max. score:
3
Reversibility:
not fully reversible within: the shortened observation period of 72 h
Remarks on result:
other: conssidered to be fully reversible within a prolonged observation period
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
other: mean of 24, 48 and 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
other: mean of 24, 48 and 72 h
Score:
1.7
Max. score:
3
Reversibility:
not fully reversible within: the shortened observation period of 72 h
Remarks on result:
other: conssidered to be fully reversible within a prolonged observation period
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
other: mean of 24, 48 and 72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean of 24, 48 and 72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean of 24, 48 and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean of 24, 48 and 72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
other: mean of 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
other: mean of 24, 48 and 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
other: mean of 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: Reversibility is inapplicable since no signs of irritation (chemosis) were observed at any time
Irritant / corrosive response data:
discharge was noted for all animals 24 h after instillation which was still existent in 1 animal until the end of the observation period.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material is slightly irritating to the eyes under the test conditions which are basically in accordance with today’s standard methods regarding dosing, exposure duration, scoring system and reading time points. 2 animals showed a conjunctival redness score of one and 1 animal slight discharge until the end of the 72 h observation period. All other signs of irritation were fully reversible within 72 h.

Based on the slightness of the observed conjunctival effects and because of their proceeding recovery full reversibility is expected in the course of a prolonged recovery period in all animals.

Therefore, the slight effect does not result in a classification of the test item according to the classification criteria of Regulation (EC) No 1272/2008.
Executive summary:

The test substance was subject to a test of eye irritancy according to FDA guidelines ( Federal Register 38, No. 187, 27.9.1973, p 27019). 100 mg of substance were applied to one eye of six animals each. The eyes were washed 24 h after application and eye responses were monitored for 72 h after start of the exposure. The calculated mean scores showed differing degrees of severity but were all well below the threshold for classification. Beside that a slight discharge was observed which still persists in 1 animal up to the 72 h reading. Conjunctiva redness scores of 1 were observed in 2 animals at reading time point 72h (= not fully reversible within the observation period). Based on the slightness of the observed conjunctival effects and because of their proceeding recovery full reversibility is expected for these 2 animals in the course of a prolonged recovery period.

Therefore, the test item has not to be classified for eye irritation according to Regulation (EC) No 1272/2008.