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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Internationally accepted guideline, well documented and scientifically acceptable.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Principles of method if other than guideline:
Test was conducted according to the Proposed Guidelines of the United States Environmental Protection Agency (EPA) § 163.81-4 "Primary eye irritation study", Federal Register, Vol. 43, No. 163, August 22, 1978.
GLP compliance:
no
Remarks:
Pre GLP

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: IVANOVAS, 7964 Kisslegg/Allgäu, Germany and MADOERIN AG, 4414 Füllinsdorf, Switzerland.
- Age at study initiation: adult, age not specified.
- Weight at study initiation: 2 to 3 kg.
- Housing: housed individually in metal cages.
- Diet: ad libitum, standard rabbit food - NAFAG, No. 814, Gossau SG.
- Water: ad libitum.
- Acclimation period: prior to treatment they were adapted to our laboratories for a minimum of 4 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Relative humidity: 55 ± 10 %
- Photoperiod: 10 hours light cycle day.

Test system

Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 ml.
- Application: test substance was inserted into the conjunctival sac of the left eye of the rabbits and the lids were gently closed for a few seconds.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
Three males and three females.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: in 3 of the 6 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 ml of physiological saline.

TOOL USED TO ASSESS SCORE
The eye irritation was appraised with a slit-lamp on day 1, 2, 3, 4 and 7.

SCORING SYSTEM

Cornea
A Opacity-degree of density (area most dense taken for reading)
No opacity: 0
Scattered or diffuse area, details of iris clearly visible: 1
Easily discernible translucent areas, details of iris slightly obscured: 2
Opalescent areas, no details of iris visible, size of pupil barely discernible: 3
Opaque, iris invisible: 4
B Area of cornea involved
One quarter (or less) but not zero: 1
Greater than one quarter, but less than half: 2
Greater than half, but less than three quarters: 3
Greater than three quarters, up to whole area: 4
A x B x 5 Total maximum = 80

Iris
A Values
Normal: 0
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination of any thereof) iris still reacting to light (sluggish reaction is positive): 1
No reaction to light, hemorrhage, gross destruction (any or all of these): 2
A x 5 Total maximum = 10

Conjunctivae
A Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal: 0
Vessels definitely injected above normal: 1
More diffuse, deeper crimson red, individual vessels not easily discernible: 2
Diffuse beefy red: 3
B Chemosis
No swelling: 0
Any swelling above normal (includes nictitating membrane): 1
Obvious swelling with partial eversion of lids: 2
Swelling with lids about half closed: 3
Swelling with lids about half closed to completely closed: 4
C Discharge
No discharge: 0
Any amount different from normal (does not include small amounts observed in inner canthus of normal animals): 1
Discharge with moistening of the lids and hairs just adjacent to lids: 2
Discharge with moistening of the lids and hairs, and considerable area around the eye: 3
(A + B + C) x 2 Total maximum = 20

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: 6/6
Time point:
other: mean 24, 48, 72 hours
Score:
< 1
Reversibility:
fully reversible
Remarks on result:
other: rinsed and unrinsed eyes
Irritation parameter:
iris score
Basis:
animal: 6/6
Time point:
other: mean 24, 48 and 72 hours
Score:
< 1
Reversibility:
fully reversible
Remarks on result:
other: rinsed and unrinsed eyes
Irritation parameter:
conjunctivae score
Basis:
animal: 6/6
Time point:
other: mean 24, 48 and 72 hours
Score:
< 2
Reversibility:
fully reversible
Remarks on result:
other: rinsed and unrinsed eyes
Irritation parameter:
chemosis score
Basis:
animal: 6/6
Time point:
other: mean 24, 48 and 72 hours
Score:
< 2
Reversibility:
fully reversible
Remarks on result:
other: rinsed and unrinsed eyes
Irritant / corrosive response data:
The substance was found to cause no irritation when applied to the rabbit eye mucosa.

Any other information on results incl. tables

Rabbit eye irritation scores

Animal Eye 24 hrs 48 hrs 72 hrs 4 days 7 days Mean 24, 48, 72 hrs

Cornea

274 eye not rinsed 0 0 0 0 0 0.00
275 eye not rinsed 0 0 0 0 0 0.00
276 eye not rinsed 0 0 0 0 0 0.00
277 rinsed after 30 sec. 0 0 0 0 0 0.00
278 rinsed after 30 sec. 0 0 0 0 0 0.00
279 rinsed after 30 sec. 0 0 0 0 0 0.00

Iritis

274 eye not rinsed 0 0 0 0 0 0.00
275 eye not rinsed 0 0 0 0 0 0.00
276 eye not rinsed 0 0 0 0 0 0.00
277 rinsed after 30 sec. 0 0 0 0 0 0.00
278 rinsed after 30 sec. 0 0 0 0 0 0.00
279 rinsed after 30 sec. 0 0 0 0 0 0.00

Conjunctival redness

274 eye not rinsed 0 0 0 0 0 0.00
275 eye not rinsed 0 0 0 0 0 0.00
276 eye not rinsed 0 0 0 0 0 0.00
277 rinsed after 30 sec. 0 0 0 0 0 0.00
278 rinsed after 30 sec. 0 0 0 0 0 0.00
279 rinsed after 30 sec. 0 0 0 0 0 0.00

Conjunctival chemosis

274 eye not rinsed 0 0 0 0 0 0.00
275 eye not rinsed 0 0 0 0 0 0.00
276 eye not rinsed 0 0 0 0 0 0.00
277 rinsed after 30 sec. 0 0 0 0 0 0.00
278 rinsed after 30 sec. 0 0 0 0 0 0.00
279 rinsed after 30 sec. 0 0 0 0 0 0.00

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information according to the CLP Regulation Criteria used for interpretation of results: EU
Conclusions:
Not irritating.
Executive summary:

Method

Test was conducted following the procedure used is described in the Proposed Guidelines of the United States Environmental Protection Agency (EPA) § 163.81-4 "Primary eye irritation study", Federal Register, Vol. 43, No. 163, August 22, 1978.

Results

The substance was found to cause no irritation when applied to the rabbit eye mucosa.

Conclusion

According to the CLP Regulation (EC 1272/2008), the substance can be classified as not irritating, because when applied to the eye of an animal does not produce at least in 2 of 3 tested animals, a positive response of corneal opacity ≥ 1 and/or iritis ≥ 1, and/or conjunctival redness ≥ 2 and/or conjunctival oedema (chemosis) ≥ 2, calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material.