Oxirane, 2,2'-[methylenebis[(2,6-dimethyl-4,1-phenylene)oxymethylene]]bis-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 September 2006 to 11 November 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

439-910-1

EC Name:

-

Cas Number:

93705-66-9

Molecular formula:

C23H28O4

IUPAC Name:

2-{[4-({3,5-dimethyl-4-[(oxiran-2-yl)methoxy]phenyl}methyl)-2,6-dimethylphenoxy]methyl}oxirane

Test material form:

solid

Details on test material:

- Appearance: white solid
- Storage conditions 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:

TEST ANIMALS
- Age at study initiation: 12 - 20 weeks
- Weight at study initiation: 2.0 - 3.5 kg
- Housing: animals were individually housed in suspended cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17 - 23 °C
- Humidity: 30 - 70 %
- Air changes: at least fifteen changes per hour
- Photoperiod: 12 hours light and 12 hours dark

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL (57 mg)

Duration of treatment / exposure:

Test material 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 material, and then released.

Observation period (in vivo):

Immediately after administration of the test material, an assessment of the initial pain reaction was made. Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment.

Number of animals or in vitro replicates:

3

Initially, a single rabbit was treated. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.

Details on study design:

- Measurement of pH
The pH of the test material was determined prior to commencement of the study. a 10% w/w aqueous preparation of the test material was found to have a pH of ca 9.

- In vivo study
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.
In order to minimise pain on application of the test material, one drop of local anaesthetic (Tetracaine hydrochloride 0.5 %) was instilled into both eyes of these animals 1 to 2 minutes before treatment.

SCORING SYSTEM: Assessment of ocular damage/irritation was made according to the Draize scale.
Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within:

Remarks:

48 hours

Results 5

Irritation parameter:

conjunctivae score

Remarks:

discharge

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No corneal or iridial effects were noted during the study.
Minimal conjunctival irritation was noted in all treated eyes one and 24 hours after treatment. All treated eyes appeared normal at the 48-hour observation.

Applicant's summary and conclusion

Interpretation of results:

other: Not classified according to EU criteria

Conclusions:

Under the conditions of the study the test material was found not to be irritating to eyes.

Executive summary:

The potential of the test material to cause irritation to the eye of New Zealand White Rabbits was determined in accordance with the standardised guidelines OECD 405 and EU Method B.5, under GLP conditions.

During the study 0.1 mL (57 mg) test material was instilled in to the right eye of three rabbits. The left eyes remained untreated and served as controls. Immediately after administration of the test material, an assessment of the initial pain reaction was made. Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment. Assessment of ocular damage/irritation was made according to the Draize scale. Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

No corneal or iridial effects were noted during the study.

Minimal conjunctival irritation was noted in all treated eyes one and 24 hours after treatment. All treated eyes appeared normal at the 48-hour observation.

Therefore, under the conditions of the study the test material was found not to be irritating to eyes.