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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 February to June 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Purity of the tested substance was not provided

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report date:
1980

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
other: protocol #RE(7/23/79) supplied by IFF, based on the procedure originally suggested by Draize.,H.J. "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics", Assoc. of Food and Drug Officials of the U.S., Austin, Texas (1959).
Deviations:
not specified
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
-Purity of the substance was not provided; No observation made at 1 hour post-dosing.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
Name of the substance as cited in the report: IFF #: 80-004-02
Description: white crystals
See details in the attached document to the section "Attached background material".

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Six healthy young adult albino New Zealand type rabbits with body weights in the range of 2.0 to 3.5 kg at the preliminary eye examination were used. The animals were individually numbered and the identification was marked in the ear of each rabbit by a metal tag as well as being written on the cage card. Animals were assigned to the study at random and the entire group was indicated by colour code on the cage card.

The animals were housed singly under standard laboratory conditions. They were fed 100 grams of Purina Rabbit Chow supplemented by whole oats daily, and were allowed water ad libitum. The criteria used for housing and maintenance were those specified in the ‘Guide for the Care and Use of Laboratory Animals’ (DHEW Publication No. (NIH) 78—23, Revised 1978). No extraneous material, such as sawdust or woodchips was used in the cages. The suspended pans beneath the cages were littered with prepared bedding (Easi Litter).

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
The test article was crushed into a powder with a mortar in a pestle for this study.
0.1 g of the test article 80-004-02 was applied once to the right eye of each of six rabbits.
Duration of treatment / exposure:
Single exposure.
Observation period (in vivo):
24, 48 and 72 hours and at 4, 7 days after dosing. In addition any persistent changes observed on day 7 were re-evaluated on day 10 using a hand held ophthalmoscope and the fluorescein method.
Number of animals or in vitro replicates:
six albino New Zealand rabbits
Details on study design:
Twenty-four hours prior to dosing, both eyes were examined using a hand held ophthalmoscope and then by fluorescein staining. One drop of Fluorescein Sodium Ophthalmic Solution USP was dropped onto the cornea which was then irrigated with Sodium Chloride Solution USP. The eyes were examined for corneal ulceration using an ultraviolet light. Animals used in the study were selected to be free of apparent ocular defects.
On the day of dosing, the lower lid was everted from the eyeball of the right eye to form a cup into which the test article was placed at the specified dose. The eyelid was then gently held together for one second. The eye was not washed after application of the test article. Any untoward reaction to application of test substance was noted and the animal was returned to its cage.
Both eyes were scored according to the Draize Method at 24, 48 and 72 hours and at 4 and 7 days after dosing. In addition at 24 hours and 7 days, both eyes were examined with fluorescein stain under an ultraviolet light.

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 one 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
Vessels 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

Classification Scale:
0.0-0.5 non-irritating
0.6-10.0 practically non-irritating
10.1-25.0 mildly irritating
25.1-50.0 moderately irritating
50.1-110.0 extremely irritating

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3, #4, #5 and #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3, #4, #5 and #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: #1, #2, #3, #4, #5 and #6
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal: #1, #2, #3, #4, #5 and #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
animal: #1, #2, #3, #4, #5 and #6
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
None of the dosed eyes had any reaction during the 7 day observation period. All eyes were negative for fluorescein retention.

The mean ocular irritation scores were:
0 at 24 hours
0 at 48 hours
0 at 72 hours
0 at 4 days
0 at 7 days
Other effects:
None.

Any other information on results incl. tables

The Primary Ocular Irritation Scores were 0 at all readings; therefore, the test article was classified as non-irritating to the eye of the albino rabbit.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information under CLP REGULATION (EC) No 1272/2008 Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL
Conclusions:
The Primary Ocular Irritation Scores were 0 at all readings; therefore, the test article was classified as non-irritating to the eye of the albino rabbit.
Executive summary:

The results of this study demonstrated that administration of heliotropin (piperonal) (0.1 g) to the eyes of rabbits is not irritating; the primary ocular irritation score was 0 for all animals at all evaluation timepoints up to and including 7 days post-dosing.