Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was carried out in compliance with Directive 92/69/EEC, Annex B.5 "Acute Toxicity - Eye Irritation", 1992, and OECD Guideline for Testing of Chemicals, No. 405 "Acute Eye Irritation/Corrosion", 1987 with no deviations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Swiss Federal Department of the Interior

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Actinol
- Physical state: crystalline white powder
- Analytical purity: 99.5 %
- Lot/batch No.: 410016
- Expiration date of the lot/batch: 31 July 2000
- Storage condition of test material: at room temperature, protected from sun light
- Other:

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Elevage Scientifique des Dombes, Chatillon sur Chalaronne, France
- Age at study initiation: 14 weeks
- Weight at study initiation:
- Housing: individual stainless steel cages equipped with feed hoppers, drinking bowls, with wood and haysticks for gnawing
- Diet (e.g. ad libitum): pelleted Provimi Kliba 3418 (batch no. 65/99) ad libitum
- Water (e.g. ad libitum): community tap water Füllinsdorf, ad libitum
- Acclimation period: one week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: To:

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
On the day of treatment, the test substance (undiluted) was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of test subtance. The right eye remained untreated and served as the reference control.
Observation period (in vivo):
7 September to 16 September 1999, 72 hours during experiment
Number of animals or in vitro replicates:
one male, two females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done):
- Time after start of exposure:


SCORING SYSTEM:
The ocular reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, 1992 at approximately 1, 24, 48 and 72 hours after administration.

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein
Eye examinations were made with a Varta Cliptrix diagnostic lamp (A. Riegger, Basel, Switzerland)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
other: primary irritation score
Basis:
mean
Time point:
other: 24-72 hours after administration
Score:
0.89
Max. score:
13
Reversibility:
fully reversible within: 72
Remarks:
h
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 72
Remarks:
h
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.75
Max. score:
3
Reversibility:
fully reversible within: 72
Remarks:
h
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.5
Max. score:
3
Reversibility:
fully reversible within: 72
Remarks:
h
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.25
Max. score:
3
Reversibility:
fully reversible within: 24
Remarks:
h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.5
Max. score:
3
Reversibility:
fully reversible within: 24
Remarks:
h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.25
Max. score:
3
Reversibility:
fully reversible within: 24
Remarks:
h
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.75
Max. score:
3
Reversibility:
fully reversible within: 72
Remarks:
h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.75
Max. score:
3
Reversibility:
fully reversible within: 72
Remarks:
h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.5
Max. score:
3
Reversibility:
fully reversible within: 48
Remarks:
h
Irritant / corrosive response data:
Scattered areas of corneal opacity were seen in two animals one hour after treatment and persisted 24 to 48 hours. Hyperemic conjunctival blood vessels were noted in all animals at the 1-hour examination and persisted 24 hours in one female or 48 hours in the two other animals. Swelling of the conjunctivae with/without partial eversion of eye lids and swelling of the nictitating membrane was observed one hour after treatment in all animals. Slightly reddened sclera was observed from the 1 through 48 hours after treatment in one male and one female and also in the other female at the 24-hour reading. Moderate watery discharge was found in both females at the 1-hour reading. All eye reactions were clear within 72 hours after treatment.
No staining of the treated eyes by the test substance was observed. No corrosion of the cornea was observed at any of the reading times.
Other effects:
No clinical signs or systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred. The bodyweight of all rabbits was considered to be within the normal range of variability.

Any other information on results incl. tables

no remarks

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based upon the referred classification criteria, Actinol is considered to be "not irritating" to the rabbit eye.
Executive summary:

The primary irritation potential of the test substance Actinol was investigated by instillation of 0.1 g into one eye of each of three young adult New Zealand White rabbits in accordance with Directive 92/69/EEC, B.5, 1992, and OECD Guideline No. 405, 1987. The treated eyes were not rinsed after application. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after the test substance's application. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion.

The primary irritation score was calculated by totaling the individual cumulative scores at 24, 48 and 72 hours and then dividing the resulting score by the number of data points. The primary irritation score was 0.89 (maximum 13).

Scattered areas of corneal opacity were seen in two animals one hour after treatment and persisted 24 to 48 hours. Hyperemic conjunctival blood vessels were noted in all animals at the 1-hour examination and persisted 24 hours in one female or 48 hours in the two other animals. Swelling of the conjunctivae with/without partial eversion of eye lids and swelling of the nictitating membrane was observed one hour after treatment in all animals. Slightly reddened sclera was observed from the 1 through 48 hours after treatment in one male and one female and also in the other female at the 24-hour reading. Moderate watery discharge was found in both females at the 1-hour reading. All eye reactions were clear within 72 hours after treatment. No staining of the treated eyes by the test substance was observed. No corrosion of the cornea was observed at any of the reading times.

Based upon the referred classification criteria (Directive 93/21/EEC, 1993), Actinol is considered to be "not irritating" to the rabbit eye.