Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24/11/2008 to 30/12/2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP in accordance with recognised guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

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 (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
No further information required.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK.
- Age at study initiation: Twelve to twenty weeks old
- Weight at study initiation: 2.0 to 3.5 kg
- Housing: The animals were individually housed in suspended cages.
- Diet (e.g. ad libitum): Free access to food (2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study.
- Acclimation period: Minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): Lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Test system

Vehicle:
water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied:
A volume of 0.1 ml of the test material, which was found to weigh approximately 65 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye.
Duration of treatment / exposure:
n/a
Observation period (in vivo):
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment. Additional observations were made on Days 7, 14 and 21 to assess the reversibility of the ocular effects.
Number of animals or in vitro replicates:
3 male rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not specified
- Time after start of exposure: n/a

SCORING SYSTEM:
Using the numerical data obtained a modified version of the system described by Kay J H and Calandra J C (1962), J. Soc. Cosmet. Chem. 13, 281-289 and 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
Basis:
mean
Time point:
other: Mean overall score for 24, 48 and 72 hrs
Score:
0
Reversibility:
other: No effects
Irritation parameter:
iris score
Basis:
mean
Time point:
other: Mean overall score for 24, 48 and 72 hrs
Score:
0
Reversibility:
other: No effects
Irritation parameter:
conjunctivae score
Remarks:
(Redness)
Basis:
mean
Time point:
other: Mean overall score for 24, 48 and 72 hrs
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 72 hrs
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: Mean overall score for 24, 48 and 72 hrs
Score:
0.56
Max. score:
1
Reversibility:
fully reversible within: 72 hrs
Irritation parameter:
conjunctivae score
Remarks:
(Discharge)
Basis:
mean
Time point:
other: Mean overall score for 24, 48 and 72 hrs
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48 hrs
Irritant / corrosive response data:
One treated eye appeared normal at the 14-day observation and the remaining treated eyes appeared normal at the 21-day observation.
Other effects:
Blue coloured staining of the fur was noted around all treated eyes throughout the study.
Blue coloured staining of the lower half of the cornea and on the nictitating membrane was noted in two treated eyes at the 24-hour observation, in all treated eyes at the 48, 72-hour and 7-day observations and persisted in two treated eyes at the 14-day observation. The staining did not affect evaluation of the ocular effects.

Any other information on results incl. tables

No corneal or iridial effects were noted during the study.

Moderate conjunctival irritation was noted in all treated eyes one and 24 hours after treatment with minimal conjunctival irritation noted at the 48-hour observation.

Blue coloured staining of the fur was noted around all treated eyes throughout the study.

Blue coloured staining of the lower half of the cornea and on the nictitating membrane was noted in two treated eyes at the 24-hour observation, in all treated eyes at the 48, 72-hour and 7-day observations and persisted in two treated eyes at the 14-day observation. The staining did not affect evaluation of the ocular effects.

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information (Mild Irritant) Criteria used for interpretation of results: other: Modified Kay and Calandra Classification system
Conclusions:
The test material produced a maximum group mean score of 12.0 and was classified as a MILD IRRITANT (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.
Executive summary:

In an Acute eye irritation in the rabbit study (Harlan project number: 0959/0229) the test material was classified as a MILD IRRITANT (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The study was performed to assess the irritancy potential of the test material following a single application to the rabbit eye. The method was designed to meet the requirements of the following:

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

- Method B5 Acute Toxicity (Eye Irritation) of Commission Directive 2004173/EC.

Blue coloured staining of the lower half of the cornea and on the nictitating membrane was noted in two treated eyes at the 24-hour observation, in all treated eyes at the 48, 72-hour and 7-day observations and persisted in two treated eyes at the 14-day observation. The staining did not affect evaluation of the ocular effects.

No corneal or iridial effects were noted during the study.

Moderate conjunctival irritation was noted in all treated eyes one and 24 hours after treatment with minimal conjunctival irritation noted at the 48-hour observation.

One treated eye appeared normal at the 14-day observation and the remaining treated eyes appeared normal at the 21-day observation.

All animals showed expected gain in bodyweight during the study.