Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions Restrictions compared to OECD 405 (adopted 1987): - 14 hour instead of 12 hours light cycle - individual scores for redness and chemosis are missing

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1976
Report date:
1976

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
other: eye irritants described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959), the US Association of Food and Drug Officials (AFDO)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
- 14 hour instead of 12 hours light cycle - individual scores for redness and chemosis are missing
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(1,2,2,6,6-pentamethyl-4-piperidyl) [[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]butylmalonate
EC Number:
264-513-3
EC Name:
Bis(1,2,2,6,6-pentamethyl-4-piperidyl) [[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]butylmalonate
Cas Number:
63843-89-0
Molecular formula:
C42H72N2O5
IUPAC Name:
bis(1,2,2,6,6-pentamethylpiperidin-4-yl) butyl(3,5-di-tert-butyl-4-hydroxybenzyl)malonate
Details on test material:
- Analytical purity: no data provided
- Lot/batch No.: EN 6003

Test animals / tissue source

Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.5 to 2 kg
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 1
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 10/14

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
in 3 of 6 rabbits: 30 sec
in 3 of 6 rabbits: eyes were not washed out
Observation period (in vivo):
up to 7 days
Number of animals or in vitro replicates:
3 male and 3 female
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): in half of the rabbits eyes were flushed with lukewarm water
- Time after start of exposure: 30 seconds

SCORING SYSTEM: Eye reactions were evaluated and scored according to Draize ("Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics", Ass Food Drug Officials, USA, 1959, page 46).
The following numerical scoring system was used to grade the eye lesions:
CORNEA:
A Opacity and degree of density (most dense area scored)
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 Maximum possible score = 80

IRIS;
A Values
Normal: 0
Folds above normal, congestion, swelling, circumcornea 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 Maximum possible score = 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 Maximum possible score = 20

TOOL USED TO ASSESS SCORE: hand-slit lamp

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
iris score
Basis:
mean
Remarks:
3 animals
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
10
Reversibility:
other: not applicable
Remarks on result:
other: eyes not washed out
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
3 animals
Time point:
other: 24, 48, 72 hours
Score:
0.6
Max. score:
80
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: eyes not washed out
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
3 animals
Time point:
other: 24, 48, 72 hours
Score:
2.67
Max. score:
20
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: (eyes not washed out): includes redness, chemosis and discharge, no individual scores available
Irritant / corrosive response data:
Cornea Score (eyes not washed out): only one animal showed after 24 hours a score of 1, which was not seen after 48 hours anymore.
Conjunctivae Score (eyes not washed out): only one animal showed conjunctival irritation until 72 hours after treatment. The other two animals did not show any irritations.

When eyes were washed out after 30 seconds no irritation were found at all.

Any other information on results incl. tables

Scores:

 Days after Appl.     Rabbit 4 (female)       Rabbit 5 (female)      Rabbit 6 (female)   
Cornea  Iris Conjunct.  Cornea  Iris  Conjunct.  Cornea  Iris  Conjunct. 
 1  5 10 
 2
 3
 4 0 0 0
 7 0

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information
Conclusions:
Since conjunctival irritation is only found in one animal and was fully reverible within 4 days it can be concluded that the test substance is not irritating.

Categories Display