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

Endpoint summary

Description of key information

Skin irritation

Under the conditions of this study the test material was determined to be non-irritating to the skin.

Eye irritation

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

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05 July 2006 to 31 August 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system 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 (hrs dark / hrs light): 12 hours light and 12 hours dark

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Remarks:

the test material was moistened with 0.5 mL of distilled water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5g of test material moistened with 0.5 mL of distilled water

Duration of treatment / exposure:

3 minutes, 1 and 4 hours

Observation period:

72 hours following patch removal

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: On the day before the test each rabbit was clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study. On the day before the test each rabbit was clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.
- Type of wrap if used: Each patch was secured in position with a strip of surgical adhesive tape. To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset and the animal was returned to its cage for the duration of the 1 and 4 hour exposure periods.

REMOVAL OF TEST SUBSTANCE
One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application. Any residual test material was removed by gentle swabbing with cotton wool soaked in distilled water.

OBSERVATION TIME POINTS
Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the Draize scale.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

- 3-Minute Exposure Period: No evidence of skin irritation was noted during the study.
- 1-Hour Exposure Period: No evidence of skin irritation was noted during the study.
- 4-Hour Exposure Period: No evidence of skin irritation was noted during the study.

Interpretation of results:

other: Not classified according to EU criteria

Conclusions:

Under the conditions of this study the test material was determined to be non-irritating to the skin.

Executive summary:

The potential of the test material to cause irritation to the skin was determined in accordance with the standardised guidelines OECD 404 and EU Method B.4, under GLP conditions, using an in-vivo method.

During the study, three New Zealand White rabbits were treated with the test material under a semi-occlusive dressing for 3 minutes, 1 hour and four hours. After the removal of the test material the skin was observed at 1, 24, 48 and 72 hours for cutaneous irritation.

No signs of irritation were noted.

Under the conditions of this study the test material was determined to be non-irritating to the skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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

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.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

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

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The potential of the test material to cause irritation to the skin was determined in accordance with the standardised guidelines OECD 404 and EU Method B.4, under GLP conditions, using an in-vivo method. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

During the study, three New Zealand White rabbits were treated with the test material under a semi-occlusive dressing for 3 minutes, 1 hour and four hours. After the removal of the test material the skin was observed at 1, 24, 48 and 72 hours for cutaneous irritation.

No signs of irritation were noted.

Under the conditions of this study the test material was determined to be non-irritating to the skin.

Eye irritation

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. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

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.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance does not require classification with respect to skin corrosion/ irritation or eye irritation.