Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD, EPA, etc)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): XP-7866
- Substance type: White powder
- Physical state: Solid
- Analytical purity: 99.5 wt% obtained by H-NMR
- Purity test date: 99.5 wt%
- Lot/batch No.: 10188-1 JM
- Expiration date of the lot/batch: February 28, 2015
- Storage condition of test material: Room temperature in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
EST ANIMALS
- Source: New Zealand White (Hsdlf:NZW) strain rabbits, supplied by Harlan Laboratories UK Ltd., Leicestershire, UK.
- Age at study initiation: twelve to twenty weeks old at the start of the study.
- Weight at study initiation: 2.21 to 3.08 kg at the start of the study.
- Housing: Animals were individually housed in suspended cages.
- Diet (e.g. ad libitum): free access
- Water (e.g. ad libitum): free access
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C
- Humidity (%): 30 to 70%
- Rate of air changes (per hr): Fifteen changes per hours
- Photoperiod (hrs dark / hrs light): 12h/12h light/darkness (0.6:00 to 18:00)

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: Left eye untreated
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): A volume of 0.1 ml of the test item, which was found to weigh approximately 70 mg (as measured by gently compacting the required volume into an adapted syringe).


Note:
* The absorption of the test item was not determined.
*The pH of the test item was determined prior to commencement of the study. the pH was for a preparation of 10% w/w aqueous preparation of the test item: 7.3 immediately and 7.6 after 10 minutes.
Duration of treatment / exposure:
single application to the test item to the non-irrigated eye.
Observation period (in vivo):
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following the treatment.
Number of animals or in vitro replicates:
Three rabbits
Details on study design:
TEST APPLICATION:
Initially, a single rabbit was treated. The test item was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the
test item, and then released. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not done

SCORING SYSTEM:
* Initial pain reaction:
Class 0: No response --> No initial pain
Class 1: A few blinks only, normal within one or two minutes --> Practically no initial pain
Class 2: Rabbit blinks and tries to open eye, but --> Slight initial pain
Class 3: Rabbit holds eye shut and puts pressure on lids, may rub eye with paw --> Moderate initial pain
Class 4: Rabbit holds eye shut vigorously, may squeal --> Severe initial pain
Class 5: Rabbit holds eye shut vigorously, may squeal, claw at eye, jump and try to escape --> Very severe initial pain

* Acute eye irritation in the rabbit:
Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49

TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
Degree of opacity
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Reversibility:
other: Not applicable in this case
Irritation parameter:
cornea opacity score
Remarks:
Degree of opacity
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Reversibility:
other: Not applicable in this case
Irritation parameter:
cornea opacity score
Remarks:
Degree of opacity
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Reversibility:
other: Not applicable in this case
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Reversibility:
other: Not applicable in this case
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Reversibility:
other: Not applicable in this case
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Reversibility:
other: Not applicable in this case
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
0.66
Max. score:
1
Reversibility:
fully reversible
Remarks:
after 72 hours
Remarks on result:
other: The score after 1 hour was 2
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
0.66
Max. score:
1
Reversibility:
fully reversible
Remarks:
after 72 hours
Remarks on result:
other: The score after 1 hour was 2
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
0.66
Max. score:
1
Reversibility:
fully reversible
Remarks:
after 72 hours
Remarks on result:
other: The score after 1 hour was 2
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
0.33
Max. score:
1
Reversibility:
fully reversible
Remarks:
after 48 hours
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
0.33
Max. score:
1
Reversibility:
fully reversible
Remarks:
after 48 hours
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
0.33
Max. score:
1
Reversibility:
fully reversible
Remarks:
after 48 hours
Irritant / corrosive response data:
According the experiment, the test item appears sightly irritant to eye but no effect after 72 hours observation.
Other effects:
No systemic effect observed based on bodyweight results.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Regarding the results of the experiment, the test item appears sightly irritant to rabbit eye but not sufficiently irritant for classification according to the criteria fixed by the EUROPEAN REGULATION (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.
Executive summary:

Introduction.

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit. The method was designed to be compatible with the following:

• DECO Guidelines for the Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion" (adopted 24 April 2002)

• Method 85 Acute Toxicity (Eye Irritation) of Commission Regulation (EC) No. 440/2008

Result.

A single application of the test item to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. All treated eyes appeared normal at the 72-Hour observation.

Conclusion.

Regarding the results of the experiment, the test item appears sightly irritant to rabbit eye but not sufficiently irritant for classification according to the criteria fixed by the EUROPEAN REGULATION (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.