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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:
10 JUL 2007 - 24 JUL 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
This study was conducted according to Good Laboratory Practice (GLP) and followed the OECD guideline for testing of Chemicals 405.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
April 24, 2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
2004
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Remarks:
Crl:KBL
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Kißlegg
- Age at study initiation: about 14 - 15 weeks
- Weight at study initiation: 3.76 kg (3 female rabbits)
- Housing: The animals were kept separately in special rabbit cages (manufacturer: Becker; type K99/30KU) placed on mobile racks.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 22 °C
- Humidity (%): 44 to 84 %.
- Air changes (per hr): air-conditioned room
- Photoperiod (hrs dark / hrs light): 12-hour light and a 12-hour dark

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Before application, the test material was ground in a mortar using a pestle.
Duration of treatment / exposure:
0.1 g of the test material was instilled into the conjunctival sac of the left eye of each animal by gently pulling the lower lid away from the eyeball to form a cup into which the test material was placed. The right eye remained untreated and served as control. After instillation, the eyelids were closed for 30 seconds.
Observation period (in vivo):
1 hour after treatment, after 24, 48, and 72 hours, then daily up to day 8 of the experimental part.
Number of animals or in vitro replicates:
3 female rabbits
Details on study design:
SCORING SYSTEM:

-- Evaluation of eye reactions

- Cornea Scores
A) Opacity-degree of density (area most dense taken for reading)

No ulceration or opacity 0

Scattered or diffuse areas of opacity (other than slight dulling
of normal lustre), details of iris clearly visible 1
Easily discernible translucent area, details of iris slightly obscured 2
Nacrous area, no details of iris visible, size of pupil barely
discernible 3
Opaque cornea, iris not discernible through the opacity 4

B) Area of cornea involved not evaluated (Rating according to the DRAIZE method)

- Iris
A) Normal 0
Markedly deepened rugae, congestion, swelling, moderate
circumcorneal hyperemia, or injection, any 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

- Conjunctivae Scores
A) Redness (refers to palpebral and bulbar conjunctivae,
cornea and iris)
Blood vessels normal 0
Some blood vessels definitely hyperemic (injected) 1
Diffuse, crimson color, individual vessels not easily discernible 2
Diffuse beefy red 3

B) Chemosis: lids and/or nictating membranes
No swelling 0
Any swelling above normal (includes nictating membranes) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids more than half closed 4

C) Discharge (Rating according to the DRAIZE method )
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 of a considerable area around the eye 3

Mean score of all animals = Mean grading for irritations of cornea, iris, and conjunctivae per time point
Mean score per animal = Mean grading for each animal of irritations of cornea, iris, and conjunctivae (1, 24, 48, and 72 hours after application)
Maximum value = Maximum grading of a sign of irritation within a period

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effect
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No signs of irritation were observed at the cornea or iris. All animals showed redness (score 1) and discharge (score 1) one hour after instillation of the test material. No abnormalities were detected in the untreated eyes.
Other effects:
None.
All animals survived the observation period. Body weight development of the treated rabbits was inconspicuous.
No signs of clinical toxicity were detected.

Any other information on results incl. tables

Pretests

Prior to testing, the pH of the test material was determined with pH-test strips. The pH was found to be about 7.

The test material was screened for its irritating potential using the hen's egg test on the chorioallantoic membrane (HET-CAM) as described below.

Fertile hens eggs, on day 10 of incubation, provided the test system. The egg shell was entered above the air cell by a dentist's rotary and then pared off. The shell with attached outer membrane and inner egg membrane was carefully opened. After the membrane had been moistened with isotonic sodium chloride solution, it was removed to expose the chorioallantoic membrane (CAM) of the fertilized egg, which lies immediately below. The CAM of fertilized and incubated hens eggs provides a suitable model for membranes with an intact and functional vascular system. The CAM has no nerve fibers in the early stages of development and is, therefore, regarded as being insensitive to pain.

In this model the cumulative irritation score of the test item was 0.00, indicating no irritant potential.

Applicant's summary and conclusion

Interpretation of results:
other: EU GHS criteria not met
Conclusions:
No eye irritating potential could be detected, thus the test material should not be classified as eye irritant according to Regulation (EC) No 1272/2008.
Executive summary:

The registered substance was tested for eye irritation in an Acute Eye Irritation / Corrosion test according to OECD Guideline 405 following GLP.

Purpose

The purpose of this primary eye irritation assay was to provide information on possible health hazards in case of acute eye contact with a test material and serve as a rational basis for risk assessment to the eye irritating potential of the test item in man.

Study Design

To test for eye irritation a test according to the OECD-Guidelines for Testing of Chemicals No. 405, the annex to Directive 92/69 EEC, and the recommendations of DRAIZE (1959) was performed.

Results

No signs of irritation were observed at the cornea or iris. One hour and 24 hours after treatment, the conjunctivae showed redness (score 1) in two animals. Furthermore, discharge (score 1) was seen one hour after treatment. Thereafter no signs of irritation were observed. The untreated eyes were unchanged.

Conclusion

No eye irritating potential could be detected, thus the test material should not be classified as eye irritant according to Regulation (EC) No 1272/2008.