Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2014-07-28 to 2014-09-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

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:
- Physical state:amber coloured viscous liquid
- Analytical purity: 100%
- Expiration date of the lot/batch: 17 March 2016
- Storage condition of test material: room temperature on the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlon Laboratories UK Ltd., Leicestershire, UK
- Age at study initiation: 12 - 20 weeks
- Weight at study initiation: 2.19 kg and 2.78 kg
- Housing: individual suspended cages
- Diet (e.g. ad libitum): 2930C Teklad Global Rabbit Diet ad libitum
- Water (e.g. ad libitum): mains drinking water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 15 changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/dark

IN-LIFE DATES: From: 2014-07-28 To: 2014-09-01

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
1, 24, 48 and 72 hours, Days 7, 14 and 21.
Number of animals or in vitro replicates:
2. The number of animals used was the minimum required to achieve the objectives of the study. Testing was conducted in two animals and the response in those animals was such that exposure of a third animal would not affect classification of the test item, therefore, no further testing was needed
Details on study design:
SCORING SYSTEM: Numerical system according to Draize

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: 24, 48 and 72 Hours
Score:
1
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 Hours
Score:
0.833
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 and 72 Hours
Score:
2
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 Hours
Score:
1.833
Max. score:
4
Reversibility:
fully reversible
Irritant / corrosive response data:
Diffuse corneal opacity was noted in both treated eyes at the 24, 48 and 72-hour observations.
Iridial inflammation was noted in both treated eyes 1 hour after treatment and at the 24 and 48-hour observations and persisted in one eye at the 72-hour observation.
Severe conjunctival irritation was noted in one treated eye with moderate conjunctival irritation noted in the other treated eye 1 hour after treatment. Moderate conjunctival irritation was noted in both treated eyes at the 24, 48 and 72-hour observations. Moderate conjunctival irritation persisted in one treated eye at the 7-day observation with minimal conjunctival irritation noted in this threated eye atthe 14-day observation.
One treated eye appeared normal at the 7-day observation and the other threated eye appeared normal at the 21-day observation.
Other effects:
Both animals showed expected gain in body weight during the study.

Applicant's summary and conclusion

Interpretation of results:
Category 2A (irritating to eyes)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item produced a maximum mean group score of 24.0 and a mean score of 2 for conjunctival redness following grading at 24, 48 and 72 hours after instillation of the test material. This observation was fully reversed within the observation period of 21 days. In accordance with CLP Regulation 1272/2008 the test material is classified as a Category 2 eye irritant: Reversible effects on the eye (Category 2).
Executive summary:

Introduction

The study was performed in accordance with OECD Guideline No. 405 and EU Method B.5 to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit.

Method

A volume of 0.1 mL of 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. The left eye remained untreated and was used for control purposes. Immediately after administration of the test item, an assessment of the initial pain reaction was made . Eight hours after test item application, a subcutaneous injection of post-dose analgesia, buprenorphine 0.01 mg/kg and meloxicam 0.5 mg/kg, was administered to provide a continued therapeutic level of systemic analgesia. The treated animal was checked for signs of pain and suffering approximately 0.5 hours later. No further analgesia was required. After consideration of the ocular responses produced in the first treated animal, a second animal was similarly treated. Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation (Draize, J.H, 1977).

Results

A single application of the test item to the non-irrigated eye of two rabbits produced diffuse corneal opacity, iridial inflammation and moderate to severe conjunctival irritation. One treated eye appeared normal at the 7 -day observation and the other treated eye appeared normal at the 21 -day observation.

Conclusion

The test item produced a maximum mean group score of 24.0 and a mean score of 2 for conjunctival redness following grading at 24, 48 and 72 hours after instillation of the test material. This observation was fully reversed within the observation period of 21 days. In accordance with CLP Regulation 1272/2008 the test material is classified as a Category 2 eye irritant: Reversible effects on the eye (Category 2).