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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:
November 9, 1981 - January 15, 1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test procedure was according to the Code of Federal Regulations 1979, title 16, § 1500.42

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Code of Federal Regulations 1979, title 16, § 1500.42
Deviations:
no
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Lot/batch No.: FTI 1164
- Expiration date of the lot/batch: At storage of 25°C, the product maintain declared activity for at least 3 months. At 5°C, the declared activity is maintained for at least a year.
- Storage condition of test material: Stability was kept by placing the test substance in refrigerator

Test animals / tissue source

Species:
rabbit
Strain:
other: Albino rabbits, Danish Landstrain
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Bred by Novo Industry A/S
- Weight at study initiation: 2 - 3 kg
- Housing: Individually in galvanized steel cages with mesh floors.
- Diet (e.g. ad libitum): Standard diet (Ewos Brood Stock Feed for rabbits and guinea pigs)
- Water (e.g. ad libitum): Automatic, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22°C
- Humidity (%): 40-60%

IN-LIFE DATES: From: 1981-11-09 To: 1981-11-16

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
- Concentration (if solution): Undiluted test material
Observation period (in vivo):
The reactions were judged 1, 24, 48 and 72 hours and 7 days after treatment.
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No washing

TOOL USED TO ASSESS SCORE:
Except for the examination at 1 hour, one drop of 1% fluorescein sodium was used for the eye examinations. The excess of fluorescein was flushed out with 0.9% sodium chloride solution.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 1 h
Score:
1.67
Max. score:
2
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1 h
Score:
3.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Remarks:
ulceration
Basis:
mean
Time point:
other: 1 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24 h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 48 h
Irritation parameter:
iris score
Basis:
mean
Time point:
24 h
Score:
0.67
Max. score:
1
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24 h
Score:
2.83
Max. score:
3
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
chemosis score
Remarks:
chemosis
Basis:
mean
Time point:
24 h
Score:
0.16
Max. score:
1
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Remarks:
ulceration
Basis:
mean
Time point:
24 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
72 h
Score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
72 h
Score:
0
Irritation parameter:
conjunctivae score
Remarks:
reddness
Basis:
mean
Time point:
other: 48/72 h
Score:
1.83
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
72 h
Score:
0
Irritation parameter:
conjunctivae score
Remarks:
ulceration
Basis:
mean
Time point:
72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
7 d
Score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
7 d
Score:
0
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
7 d
Score:
0.83
Max. score:
1
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
ulceration
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
Corneal reactions: Scattered areas of corneal opacity were seen at 1 and 24 hours in 2 and 4 rabbits respectively. No corneal opacity was noted at 48 hours.

Iris reactions: Congestion was seen at 24 hours in 2 rabbits. No iris reactions were noted at 48 hours.

Conjunctival reactions: Some hyperemic blood vessels or diffuse crimson color and swelling with lids about or more than half closed were seen at 1 hour in all the rabbits. At 24 hours the conjunctiva was diffuse crimson or beefy red in all the rabbits but no chemosis was seen. At day 7 only conjunctival reactions of score 1 were observed.

Besides the eye redness that carried a score of 1 for up to 7 days after treatment, all effects were fully reversible within 72 hours.

Applicant's summary and conclusion

Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions employed, Pancreas Trypsin Novo 3.3 special was regarded as Irritating to eyes, Category 2A. Besides the eye redness that carried a score of 1 for up to 7 days after treatment, all effects were fully reversible within 72 hours.
Executive summary:

A test for eye irritation in rabbits was performed with Pancreas Trypsin Novo 3.3 special, batch FTI 1164 in accordance with the Code of Federal Regulations 1979, title 16, § 1500.42.

The eyes of the six rabbits (three male and three females) were examined for defects 24 hours prior to the test. Just before instillation of the test substance the left eye of each rabbit was anaesthetized with two drops of 1% tetracain chloride. 0.1 g of Pancreas Trypsin Novo 3.3 special, batch FTI 1164 was placed in the left eye of each rabbit by gently pulling the lower lid away from the eye ball, and then introducing the test substance into the conjunctival sac. The lids were gently held together for one second. The right eye served as control.

The ocular reactions were recorded at 1, 24, 48, 72 hours and 7 days after instillation according to the specified guideline. Except for the examination at 1 hour, 1 drop of 1% fluorescein sodium was used.

Corneal reactions: Scattered areas of corneal opacity were seen at 1 and 24 hours in 2 and 4 rabbits respectively. No corneal opacity was noted at 48 hours.

Iris reactions: Congestion was seen at 24 hours in 2 rabbits. No iris reactions were noted at 48 hours.

Conjunctival reactions: Some hyperemic blood vessels or diffuse crimson color and swelling with lids about or more than half closed were seen at 1 hour in all the rabbits. At 24 hours the conjunctiva was diffuse crimson or beefy red in all the rabbits but no chemosis was seen. At day 7 only conjunctival reactions of score 1 were observed.

Besides the eye redness that carried a score of 1 for up to 7 days after treatment, all effects were fully reversible within 72 hours.

In conclusion, under the test conditions employed, Pancreas Trypsin Novo 3.3 special was regarded as Irritating to eyes, Category 2A.