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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 25/6/1986 to 4/8/1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: US Pharmaceutical Manufacturers Association 1977
Deviations:
yes
Remarks:
1) The observation on day 0 of the study was not performed 60 min after installation of the test substance as protocoled, but after approximately 80 min. 2) In the night of study day 13 and 14 the temperature in the animal room raised up to 28°C.
Qualifier:
according to
Guideline:
other: US EPA Pesticide Assessment Guidelines, Subdivision F $81-4 “Primary Eye Irritation”
Version / remarks:
version: Nov. 1984. EPA protocol in accordance with the FDA requirements.
Deviations:
yes
Remarks:
with the following exception: Three additional animals have been used to investigate the effect of remedial irrigation
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
impurity
Type:
impurity
Test material form:
other: clear liquid

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: The Broekman Institute, Someren, The Netherlands
- Age at study initiation: 2 to 3 months old
- Weight at study initiation: 1.9 to 2.4 grams
- Housing: individually housed in metal cages with perforated floors
- Diet (e.g. ad libitum): standard laboratory animal diet. 100g/day
- Water (e.g. ad libitum): tap water free access
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5-21 ºC
- Humidity (%): 60-85%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12h light/12h dark

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Duration of treatment / exposure:
24 hours for animals #1 to #6 (marked as no remedial irrigation applied) and 30 seconds for animals #7 to #9 (marked as remedial irrigation applied)
Observation period (in vivo):
Immediately after instillation of the test substance
70-90min after instillation
24,48 and 72h after instillation
7 and 14 days after instillation
Number of animals or in vitro replicates:
9 young adult female animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): after application, the lids were held gently together for 2 seconds and released. The treated eye was washed with 125-150 mL tepid tap-water for aprox 1 minute
- Time after start of exposure: 30 seconds

SCORING SYSTEM: The Draize scoring system

TOOL USED TO ASSESS SCORE: fluorescein

FLUORESCEIN TREATMENT: Fluorescein was used to determine the area of corneal epitheliak damage, For that purpose, a solution of 2% sodium fluorecein in water (pH adjusted to 7) was applied to both eyes.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
mean individual scores of the unwashed eyes after application (animals #1 to #6)
Time point:
24/48/72 h
Score:
0.44
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
mean individual scores of the washed eyes after application (animals #7 to #9)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 0 days
Irritation parameter:
iris score
Basis:
mean
Remarks:
mean individual scores of the unwashed eyes after application (animals #1 to #6)
Time point:
24/48/72 h
Score:
0.18
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
mean
Remarks:
mean individual scores of the washed eyes after application (animals #7 to #9)
Time point:
24/48/72 h
Score:
0.22
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
mean individual scores of the unwashed eyes after application (animals #1 to #6)
Time point:
24/48/72 h
Score:
1.33
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
mean individual scores of the washed eyes after application (animals #7 to #9)
Time point:
24/48/72 h
Score:
1.11
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
mean individual scores of the unwashed eyes after application (animals #1 to #6)
Time point:
24/48/72 h
Score:
0.44
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
mean individual scores of the washed eyes after application (animals #7 to #9)
Time point:
24/48/72 h
Score:
0.44
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
other: conjunctivae discharge
Basis:
mean
Remarks:
mean individual scores of the unwashed eyes after application (animals #1 to #6)
Time point:
24/48/72 h
Score:
0.5
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
other: conjunctivae discharge
Basis:
mean
Remarks:
mean individual scores of the washed eyes after application (animals #7 to #9)
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 7 days

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
According to the GHS and CLP criteria for classification of the eye irritancy potential, based on the grading of ocular lesions as described in OECD 405 guideline, the tested substance should not be classified for eye irritancy under the test conditions
Executive summary:

A sample of the test item was tested in the rabbit acute eye irritation/corrosion test to determine its possible irritating or corrosive effects. Approximately 0.1 mL of the test substance was instilled into one of the eyes of nine female albino rabbits, three of which subsequently received remedial irrigation. The unwashed eyes reacted to contact with the test substance by corneal damage, involving the epithelium and in some cases also the stroma, slight iridial irritation and moderate conjunctival reddening and swelling. Remedial irrigation appeared to have a positive effect on the degree of corneal injury but it hardly reduced the irritation of conjunctivae and iris. From these results a Draize score of 19.8 was obtained for unwashed eyes and 10 for remedially irrigated eyes (both at 24 hours). According to the Kay and Calandra scheme the test substance can be classified as moderately and mildly irritating, respectively. However according to the GHS (Globally Harmonized System of Classification and Labeling of Chemicals) and CLP regulation (Regulation (EC) No 1907/2006) scheme for classification of the eye irritancy potential, based on the grading of ocular lesions as described in OECD 405 guideline, the tested substance should not be classified for eye irritancy under the test conditions.