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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987
Deviations:
no
Remarks:
No deviations that impacted the integrity of the study ocurred.
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1-BUTANESULFONAMIDE, 1,1,2,2,3,3,4,4,4-NONAFLUORO-N-METHYL-
EC Number:
614-396-3
Cas Number:
68298-12-4
Molecular formula:
C5H4F9NO2S
IUPAC Name:
1-BUTANESULFONAMIDE, 1,1,2,2,3,3,4,4,4-NONAFLUORO-N-METHYL-
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material: 3M Company, Lot 3
- Expiration date of the lot/batch: 06 August, 2002
- Purity test date: 30 January, 2002

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature in the dark.
- Stability under storage conditions: Stable
- Stability under test conditions: Stable
- Solubility and stability of the test substance in the solvent/dispersant/vehicle/test medium: The test article was tested neat.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test article was uniformly ground into a powder using a mortar and pestle prior to weighing and dosing.
- Final preparation of a solid: Dosed as a powder.

FORM AS APPLIED IN THE TEST: The test article was dosed as a powder.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland
- Age at study initiation: 6 weeks old
- Weight at study initiation: 1.0-3.5 kg
- Housing: Individually in labelled cages with perforated floors
- Diet (e.g. ad libitum): Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Germany) approx. 100g. per day.
- Water (e.g. ad libitum): Free access to tap-water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 12 November, 2001, To: 26 November, 2001

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 86.8 mg of the test article.

VEHICLE: None
Duration of treatment / exposure:
A single instillation of the test article.
Observation period (in vivo):
The rabbits were observed and eyes were scored at 1, 24, 48, and 72 hours and again at 7 and 14 days post-exposure.
Number of animals or in vitro replicates:
3 rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test substance was not removed (eyes not washed) post-exposure.
- Time after start of exposure: NA

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: Fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
Mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
Mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
Mean
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 7 days
Remarks:
7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
Mean
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks:
72 hours
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
Mean
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Remarks:
7 days
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
Mean
Time point:
24/48/72 h
Score:
0.7
Max. score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks:
72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
Mean
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks:
14 days
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
Mean
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks:
7 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
Mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
Mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #3
Remarks:
Mean
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks:
7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
Mean
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Remarks:
48 hours
Irritant / corrosive response data:
Corneal opacity (scores: 1) was observed in 1/3 animals at 24, 48, and 72 hours post dose. Iritis (scores: 1) was observed in 1/3 animals at 24 and 48 hours post dose. The individual mean scores (24-72 hours) for corneal opacity were 0.0, 1.0, and 0.0. The individual mean scores (24-72 hours) for iritis were 0.0, 0.7, and 0.0. Conjunctival redness was observed in 3/3 animals at 1 (scores: 1, n=1; 2, n=2), 24 (scores: 2, n=2; 3, n=1), 48 (scores: 2, n=2; 3, n=1), and 72 (scores: 2, n=2; 3, n=1) hours post dose and was observed in 1/3 animals at 7 days post dose (score: 1). The individual mean scores (24-72 hours) for conjunctival redness were 2.0, 3.0, and 2.0.Conjunctival chemosis was observed in 3/3 animals at 1 (scores: 1), 24 (scores: 2), and 48 (scores: 1) hours post dose and in 1/3 animals at 72 hours post dose(score: 1). The individual mean scores (24-72 hours) for conjunctival chemosis were 1.0, 1.3, and 1.0. Conjunctival discharge (scores: 1) was observed in 3/3 animals at 1-hour post dose, 2/3 animals at 24 hours post dose, and 1/3 animals at 48 hours post dose. In the animal that had corneal opacity and iritis, reduced elasticity of the eyelids was noted at 72 hours and 7 days post dose. By 14 days post dose, all eyes were normal. The highest mean PII was 13.33/110 at 24 hours post dose.

Applicant's summary and conclusion

Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Conclusions:
Based on the results of the study, the test article is a severe ocular irritant (GHS Category 2A).
Executive summary:

The primary eye irritation/corrosion potential of the test article (off white solid, Lot 3) was evaluated in New Zealand White Rabbits. This study was conducted in compliance with OECD GLP. The test method was based on OECD 405 (1987) and Commission Directive 92/69/EEC B.5 (1992). The test material (86.8 mg; a volume of approximately 0.1 mL) was administered as received to the conjunctival sac of one eye of each rabbit (3 males) by gently pulling the lower eyelid away from the eye. The lids were held together for approximately one second after administration to ensure adequate distribution of the test material. The contralateral eye of each animal served as the control. The treated eye of each rabbit was examined for irritation of the cornea, iris and conjunctiva at 1, 24, 48 and 72 hours and 7 and 14 days post dose using the Draize technique. Sodium fluorescein dye procedures were used at 24 hours after dosing to improve the evaluation of the cornea. Body weights were recorded at pretest, the day of treatment, and at termination. The Primary Irritation Index (PII) was calculated.

Corneal opacity (scores: 1) was observed in 1/3 animals at 24, 48, and 72 hours post dose. Iritis (scores: 1) was observed in 1/3 animals at 24 and 48 hours post dose. The individual mean scores (24-72 hours) for corneal opacity were 0.0, 1.0, and 0.0. The individual mean scores (24-72 hours) for iritis were 0.0, 0.7, and 0.0. Conjunctival redness was observed in 3/3 animals at 1 (scores: 1, n=1; 2, n=2), 24 (scores: 2, n=2; 3, n=1), 48 (scores: 2, n=2; 3, n=1), and 72 (scores: 2, n=2; 3, n=1) hours post dose and was observed in 1/3 animals at 7 days post dose (score: 1). The individual mean scores (24-72 hours) for conjunctival redness were 2.0, 3.0, and 2.0.Conjunctival chemosis was observed in 3/3 animals at 1 (scores: 1), 24 (scores: 2), and 48 (scores: 1) hours post dose and in 1/3 animals at 72 hours post dose(score: 1). The individual mean scores (24-72 hours) for conjunctival chemosis were 1.0, 1.3, and 1.0. Conjunctival discharge (scores: 1) was observed in 3/3 animals at 1-hour post dose, 2/3 animals at 24 hours post dose, and 1/3 animals at 48 hours post dose. In the animal that had corneal opacity and iritis, reduced elasticity of the eyelids was noted at 72 hours and 7 days post dose. By 14 days post dose, all eyes were normal. The highest mean PII was 13.33/110 at 24 hours post dose. Based on the results of the study, the test article is a severe ocular irritant (GHS Category 2A).

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