Registration Dossier

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:
2001-02-15 to 2001-03-15
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP/Guideline Study
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
other: Body responsible for the test
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: Annex V
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
other: JMAFF No. 6283
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report):Consolidated Cyclohexane Dicarboxaldehydes
- Physical state:liquid
- Impurities (identity and concentrations): Cyclohexanecarboxaldehyde 0.28%, Hydroxyaldehyde 0.23%, Unknowns 0.51%
- Lot/batch No.:9-CWDY-50-O 1
- Storage condition of test material: ambient

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Covance Research Products Inc., Denver, PA
- Age at study initiation: Young adult
- Weight at study initiation: 2602 to 2757 grams
- Housing: Individual suspended wire-mesh cages.
- Diet (e.g. ad libitum): PMI Nutrition International, Inc. Certified Rabbit LabDiet® 5322 was offered at approximately 150 g per day during the study.
- Water (e.g. ad libitum): municipal water ad libitum
- Acclimation period: The animals were acclimated to laboratory conditions for a minimum of seven days prior to initiation of dosing.

ENVIRONMENTAL CONDITIONS
- Temperature: 63-72°F
- Humidity (%): 30-78%
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

IN-LIFE DATES: From: 2001-02-15 to 2001-03-15

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: Left eye served as control for each animal
Amount / concentration applied:
.1 ML
Duration of treatment / exposure:
single, unwashed exposure
Observation period (in vivo):
Both eyes of all rabbits were examined macroscopically for ocular irritation in
accordance with the method of Draize (Appendix A) at approximately one, 24, 48 and
72 hours after dosing and on study days 4, 7, 10, 17 and 21, if irritation persisted. A
direct ophthalmoscope was used during these observations to examine the corneal
tissue. In addition, both eyes were further examined at 24 hours and at all subsequent
observations with sodium fluorescein.
Number of animals or in vitro replicates:
3
Details on study design:
There was one group of three albino rabbits that received a single, unwashed
exposure. Each 0.1-ml dose of the test article was instilled into the lower
conjunctival sac of the right eye. The eyelid was held closed for approximately one
second and released. The left eye was manipulated in a similar manner as the right
eye and served as a contralateral control.
The eyes were examined for ocular reactions in accordance with the method of Draize
(Appendix A) at approximately one, 24, 48 and 72 hours after dosing and on study
days 4, 7, 10, 17 and 21, if irritation persisted. Sodium fluorescein was used to aid in
revealing possible corneal damage at 24 hours and at all subsequent observations.

Body weights were obtained and recorded on study day 0 (initiation) and at each
rabbit’s termination from the study.

After study termination, the rabbits were euthanized by intravenous injection of
euthanasia solution and discarded.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: overall at 24, 48 and 72 h
Score:
2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: overall at 24, 48 and 72 h
Score:
2.7
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: overall at 24, 48 and 72 h
Score:
2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Max. score:
3
Remarks on result:
other: Max. duration: h; Max. value at end of observation period: 1 (related to all animals)
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: overall at 24, 48 and 72 h
Score:
3
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: overall at 24, 48 and 72 h
Score:
3.7
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: overall at 24, 48 and 72 h
Score:
3
Irritation parameter:
chemosis score
Max. score:
4
Remarks on result:
other: Max. duration: h; Max. value at end of observation period: 0 (related to all animals)
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Irritation parameter:
cornea opacity score
Max. score:
2
Remarks on result:
other: Max. duration: h; Max. value at end of observation period: 2 (related to all animals)
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Irritation parameter:
iris score
Max. score:
1
Remarks on result:
other: Max. duration: 96 h; Max. value at end of observation period: 0 (related to all animals)
Irritant / corrosive response data:
Reversibility of any observed effect: Changes not fully reversible within 21 days

Any other information on results incl. tables

No remarkable body weight changes were noted during the study.

There were no deaths during the study.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
All animals were noted with positive cornea1 (grade l-2 for opacity, grade 4 for area), iridal (grade 1) and conjunctival (grade 2-3 for redness, grade 3-4 for chemosis) findings. Irritation for two animals completely subsided by study days 10 or 17. Corneal and conjunctival findings were still present at study termination for one animal. Additionally, this animal was observed with cornea1 neovascularization on study days 10 and 17. The Maximum Average Score for Consolidated Cyclohexane Dicarboxaldehydes was 41.0 at 24 hours post-instillation.
Executive summary:

The primary ocular irritation potential of Consolidated Cyclohexane Dicarboxaldehydes was evaluated in this study with New Zealand White rabbits. There was one group of three albino rabbits that received a single, unwashed exposure. Each 0.1- ml dose of the test article was instilled into the lower conjunctival sac of the right eye. The eyelid was held closed for approximately one second and released. The left eye was manipulated in a similar manner as the right eye and served as a contralateral control. The eyes were examined for ocular reactions in accordance with the method of Draize at approximately one, 24, 48 and 72 hours after dosing and on study days 4, 7, 10, 17 and 21, if irritation persisted. Sodium fluorescein was used to aid in revealing possible corneal damage at

24 hours and at all subsequent observations. All animals were noted with positive corneal (grade 1-2 for opacity, grade 4 for area), iridal (grade 1) and conjunctival (grade 2-3 for redness, grade 3-4 for chemosis) findings. Irritation for two animals completely subsided by study days 10 or 17. Corneal and conjunctival findings were still present at study termination for one animal. Additionally, this animal was observed with corneal neovascularization on study days 10 and 17. The Maximum Average Score for Consolidated Cyclohexane Dicarboxaldehydes was 41.0 at 24 hours post-instillation.