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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:
From 28 May to 24 June 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study run to a method comparable with current guidelines and to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Details on test material:
Batch No.: 902/332991/B/X/4/1
Purity: 96.9%

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 Ltd., Leicestershire, UK
- Age at study initiation: twelve to twenty weeks old
- Weight at study initiation: 2.36 to 2.43 kg
- Housing: individually housed in suspended cages
- Diet (e.g. ad libitum): Free access to mains food (2930C Teklad Global Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

IN-LIFE DATES: From To:

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
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 88 mg
- Concentration (if solution):

VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:
Duration of treatment / exposure:
8 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 males
Details on study design:
Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used.
Initially, a single rabbit was treated. A subcutaneous injection of buprenorphine 0.01 mg/kg was administered 60 minutes prior to test item application to provide a therapeutic level of systemicanalgesia. Five minutes prior to test item application, a pre-dose anaesthesia of ocular anesthetic (two drops of 0.5% tetracaine hydrochloride) was applied to each eye.
A volume of 0.1 mL of the test item, which was found to weigh approximately 88 mg (as measured by gently compacting the required volume into an adapted syringe) 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 according to the six point scale.
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 12 hours later. No further analgesia was required.
After consideration of the ocular responses produced in the first treated animal, two additional animals were 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).
Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.
Any clinical signs of toxicity, if present, were also recorded.
Additional observations were made on Days 7 and 14 to assess the reversibility of the ocular effects.
Individual body weights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: only one animal scored 1 at 1 hour
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: mean of 24, 48 and 72 hours
Score:
ca. 0.89
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: fully reversible within 72 hours in one animal and within 14 days in other two animals
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: mean of 24, 48 and 72 hours
Score:
ca. 0.67
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: fully reversible within 48 hours, 7days and 72 hours respectly
Irritant / corrosive response data:
Yellow colored staining of the fur and eyelids of the treated eye was noted in all treated eyes during the study.
No corneal effects were noted during the study.
Iridial inflammation was noted in one treated eye one hour after treatment.
Moderate conjunctival irritation was noted in two treated eyes and minimal conjunctival irritation was noted in one treated eye one hour after treatment. Moderate conjunctival irritation was noted in one treated eye and minimal conjunctival irritation was noted in two treated eyes at the 24 and 48-Hour observations. Moderate conjunctival irritation was noted in one treated eye and minimal conjunctival irritation was noted in one other treated eye at the 72-Hour observation with minimal conjunctival irritation noted in both of these treated eyes at the 7-Day observation.
Alopecia around the treated eye was noted in one animal at the 48 and 72-Hour observations.
One treated eye appeared normal at the 72-Hour observation and two treated eyes appeared normal at the 14-Day observation.
Other effects:
All animals showed expected gain in body weight during the study.

Any other information on results incl. tables

Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number and Sex

Time after

application

Cornea opacity

Iris

Conjunctivae

Redness

Chemosis

73203 Male

1 hours

24hours

48hours

72hours

0

0

0

0

0

0

0

0

1

1

1

0

1

1

0

0

73241 Male

1 hour

24 hours

48 hours

72 hours

7 days

14 days

0

0

0

0

0

0

0

0

0

0

0

0

2

1

1

1

1

0

2

1

1

1

0

0

73242 Male

1 hour

24 hours

48 hours

72 hours

7 days

14 days

0

0

0

0

0

0

1

0

0

0

0

0

2

1

1

1

1

0

1

1

1

0

0

0

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item produced a maximum group mean score of 9.0 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.
The test item was not classified as an irritant according to GHS and EC CLP 1272/2008.