Registration Dossier

Administrative data

Endpoint:
eye irritation, other
Remarks:
in vivo study, which was an Annex VII requirement at the time
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 1994 - February 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
- Name of test material (as cited in study report): Lekutherm Beschleuniger KU 6519 Neu
Specific details on test material used for the study:
Batch 3078183

Test animals / tissue source

Species:
rabbit
Strain:
other: Albino rabbit
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Dr. Zimmermann, Untergröningen, Germany
- Weight at study initiation: 2736 g, 2453 g, 2768 g
- Housing: individually in wire grating cages (area 2450 cm2, height 42 cm) without bedding
- Diet: Raiffeisen Ringfutter Kaninchen Trockenfutter 52/P, ad libitum
- Water: Community tab water from Karlsruhe; free access for the animals by daily changing of the watering-bottles
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 22 °C
- Humidity (%): 30 - 70 %
- Light - dark - rhythm: 12 : 12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: the left eye was not treated and was used for control.
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
24 h
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
1 female, 2 male
Details on study design:
The test substance was applied undiluted in a single dose of 0.1 g into the right eye to each of 3 albino rabbits.
The substance was placed into the conjunctival sac of one eye after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second in order to prevent loss of the material.
24 h after administration the eye was carefully rinsed with NaCl 0.9 % in order to remove the residual test substance. The left eye was not treated and was used for control.
Mortality, toxicological symptoms, behaviour, body weight, eye reaction according to OECD-guideline 405 were observed 1 hour after administration and then daily for the observation period of 21 days.
On the first day, on the seventh and on the 21st day after exposure the cornea was tested with fluorescein solution to detect defects.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1st hour, day 1 to 3, day 7
Score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: day 14
Score:
1.7
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: day 21
Score:
1
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1st hour
Score:
0
Reversibility:
fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: day 1 to day 3
Score:
1
Reversibility:
fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: day 7
Score:
1.3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1st hour, day 1 to 3
Score:
3
Reversibility:
fully reversible within: 16 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: day 7
Score:
2
Reversibility:
fully reversible within: 16 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: day 14
Score:
1
Reversibility:
fully reversible within: 16 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1st hour, day 1 and day 3
Score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: day 7
Score:
3.3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: day 14
Score:
1
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: day 21
Score:
0.3
Reversibility:
not fully reversible within: 21 days
Irritant / corrosive response data:
All three rabbits suffered from severe conjunctivitis combined with suppuration. Despite the medical treatment of the eyes, all three rabbits showed ocular lesions of the cornea up to the end of the study. The chemosis effects on conjunctivae are reversible in the eyes of two rabbits. One rabbit had swelling of lids up to the end of the study.
A fluorescein test to demonstrate defects of the cornea was performed on day 1, day 7 and day 21. It was positive for the test substance for all rabbits on day 1 and day 7. On day 21 this test was negative for all rabbits.
Other effects:
Two animals yelled with pain at the administration of the test substance. The test substance did not cause mortality. In the course of the experiment the body weight of all three rabbits increased.

Any other information on results incl. tables

Findings, mean value of grades of ocular lesions

Administration: test substance in the right eye

Control: untreated left eye

conjunctivae
time after administration cornea iris redness chemosis
right left right left right left right left
1st hour 3 0 0 0 3 0 4 0
day 1 3 0 1 0 3 0 4 0
day 2 3 0 1 0 3 0 3.7 0
day 3 3 0 1 0 3 0 4 0
day 4 - - - - - - - -
day 5 - - - - - - - -
day 6 3 0 1 0 3 0 3.3 0
day 7 3 0 1.3 0 2 0 3.3 0
day 8 3.7 0 1.7 0 2 0 4 0
day 9 3.7 0 1.7 0 2 0 2 0
day 10 3.7 0 1.7 0 2 0 2 0
day 11 - - - - - - - -
day 12 - - - - - - - -
day 13 3 0 1 0 1 0 1 0
day 14 1.7 0 0 0 1 0 1 0
day 15 1.7 0 0 0 1 0 1 0
day 16 1.7 0 0 0 0 0 1 0
day 17 1 0 0 0 0 0 0.7 0
day 18 - - - - - - - -
day 19 - - - - - - - -
day 20 1 0 0 0 0 0 0.3 0
day 21 1 0 0 0 0 0 0.4 1

A fluorescein-test was perfomed on day 1, day 7 and day 21 in order to demonstrate defects of the cornea. On day 1 and day 7 this test was positive for the test substance for all rabbits. On day 21 this test was negative for the test substance for all rabbits.

Exsudation was observed in the right eye of all rabbits from day 0 to day 9. The symptom was strong suppuration for all rabbits.

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Category 2 Criteria used for interpretation of results: other: EU-GHS
Conclusions:
The study was performed according to the OECD TG405 without deviations and according to the good laboratory practice principles, it is considered to be of the highest quality (reliability Klimisch 1). The criteria of validity of the test system are fulfilled. The test material did induce effects on rabbit eyes. The test material was considered to be irritating under the conditions of the test.
Executive summary:

The test substance was investigated for its potential to cause irritation in the rabbit eye according to OECD TG 405. 0.1 g of pure substance were instilled into the conjunctival sac, the untreated eye served as control. Under the conditions of this experiment the test substance was found to cause irritation when applied to the rabbit eye mucosa. No corrosion effect was observed at each of the measuring intervals. Additionally no corrosive or acute toxicological signs were observed in the animals during the test period. According to classification criteria in the European regulation (EC) No. 1272/2008, amending regulation EC no. 1907/2006 (REACh) the test substance is irritating to eyes and should be classified as eye irritant, category 2. There were no systemic intolerance reactions.