Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vitro / ex vivo
Remarks:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 February 2013 to 28 February 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed to standardised guidelines OECD 405 and EU Method B.5 and in line with GLP. The study was reported to a high standard, sufficient to assess the quality of the data presented.

Data source

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

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:
- Storage conditions: room temperature in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Strain: Hsdlf:NZW
- Sex: male.
- Age at study initiation: 12 - 20 weeks.
- Weight at study initiation: 2.40 - 2.66 kg.
- Housing: individually in suspended cages.
- Diet: rabbit diet provided ad libitum.
- Water: mains drinking water, ad libitum.
- Acclimation period: at least 5 days.

Immediately before the start of the test, both eyes of the 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.

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

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The contra lateral eye was used as an untreated control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (98 mg).
Duration of treatment / exposure:
- Dose administration: 0.1 mL of the test material was placed into the conjunctival sac of the right eye of one rabbit, by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were then held together for about 1 second immediately after treatment, to prevent loss of the test material, and then released. The left eye remained untreated and was used for control purposes. After consideration of the ocular responses and initial pain reaction in the first treated animal, a second animal was treated.
Observation period (in vivo):
Animals were observed up to 72 hours post administration.
Number of animals or in vitro replicates:
One animals initially, followed by a further animal once the irritation potential was fully assessed in the first animal.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: Irrigation was not performed.

SCORING SYSTEM:
The reactions observed 1, 24, 48 and 72 hours following treatment were scored in accordance with the criteria of Draize (1977) and assessed using a modified form of the Kay and Calandra system (1962). Any other ocular effects were also noted.

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

ADDITIONAL OBSERVATIONS
Any clinical signs of toxicity, if present, were noted.
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:
conjunctivae score
Remarks:
chemosis
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.66
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritant / corrosive response data:
No corneal or iridial effects were noted during the study.
Minimal conjunctival irritation was noted in all treated eyes one hour after treatment and at the 24 and 48 hour observations.
Both treated eyes appeared normal at the 72 hour observation.

The test material produced a maximum group mean score of 3.0 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.
Other effects:
Both animals showed expected gain in body weight during the study.

Any other information on results incl. tables

Table 3: Ocular Irritation Results

Parameter 

Animal

Male 1

Male 2

Time after treatment (hours)

1  

24

48

72

Mean*

1  

24

48

72

Mean*

Cornea:

Degree of opacity

0

0

0

0

0

0

0

0

0

0

Area of cornea involved

0

0

0

0

0

0

0

0

0

0

Iris:

Iris

0

0

0

0

0

0

0

0

0

0

Conjunctivae:

Redness

1

1

1

0

0.66

1

1

1

0

0.66

Chemosis

1

0

0

0

0

0

0

0

0

0

Discharge

0

0

0

0

0

0

0

0

0

0

* Mean at 24, 48 and 72 hours.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, the test material only elicited slight reactions in any of the animals during the course of the study that meant the test material does not require classification as an eye irritant.
Executive summary:

The eye irritation potential of the test material was determined in a GLP study which was conducted in accordance with standardised guidelines OECD 405 and EU Method B.5. During the study, 0.1 mL of test material was placed into one eye of each of two rabbits and was assessed for up to 72 hours to determine the grade of ocular reaction. No corneal or iridial effects were noted during the study. Minimal conjunctival irritation was noted in all treated eyes one hour after treatment and at the 24 and 48 hour observations. Both treated eyes appeared normal at the 72 hour observation.

Under the conditions of the test, the test material only elicited slight reactions in any of the animals during the course of the study that meant the test material does not require classification as an eye irritant.