2,2'-[ethylenebis(oxymethylene)]bisoxirane

Endpoint summary

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at the start of treatment: 11 weeks
- Weight at the start of treatment: 2.11 - 2.16 kg
- Housing: 1 animal / cage, auto flush stainless steel cages (450W x 600D x 360H (mm))
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: during the quarantine-acclimation period, all animals were observed for clinical signs once daily for 8 days in the initial test and for 10 days in the confirmatory test

ENVIRONMENTAL CONDITIONS
- Temperature (°C): measurement value: 19.1–22.1, permissible range: 18.0–24.0
- Humidity (%): measurement value: 44.8–52.1, permissible range: 30.0–70.0
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent negative control

Duration of treatment / exposure:

4 h

Observation period:

7 days

Number of animals:

3

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24 h

Score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

48 h

Score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

72 h

Score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24 h

Score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

48 h

Score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

72 h

Score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24 h

Score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

48 h

Score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

72 h

Score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Irritant / corrosive response data:

Because no corrosion or severe irritant effects were observerd in the initial test, the confirmatory test was conducted using 2 animals.

Executive summary:

This study was conducted to evaluate the potential skin irritation/corrosion after a single dermal application of the test substance, 2,2’-[ethylenebis(oxymethylene)]bisoxirane, in three 11 -week-old male New Zealand rabbits.

0.5 mL of the undiluted test substance was applied and held in contact with the skin by a semi-occlusive dressing for 4 h. Because no corrosion or servere irritant effects were observed in the initial test, the confirmatory test was conducted using 2 animals. Observation of application sites for skin response were conducted at 1, 24, 48 and 72 h after patch removal and evaluated according to the Draize's method. In both the initial and confirmatory tests, skin irritation was observed at 72 h after application. Therefore, additional dermal observations were conducted until Day 7.

In both the initial and confirmatory tests, erythema was observed at the test substance sites from 1 h after patch removal. Erythema was no longer observed on Day 7. The primary skin irritation index (P.I.I.) of the test substance was 1.5.

In both the initial and confirmatory tests, the control sites of all animals did not reveal any evidence of adverse skin reactions such as erythema or edema during the observation period.

During the observation period, no abnormal clinical signs or body weight gain was observed in any animal.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at start of treatment: 11 weeks
- Weight at start of treatment: 2.15-2.21 kg
- Housing: 1 animal / cage, Stainless wire mesh cages (450W x 600D x 360H (mm))
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: during the quarantine-acclimation period, all animals were observed for clinical
signs once daily for 8 days in the initial test and for 10 days in the confirmatory test

ENVIRONMENTAL CONDITIONS
- Temperature (°C): measurement: 19.1–22.1, permissible range: 18.0–24.0
- Humidity (%): measurement: 43.2–54.1, permissible range: 30.0–70.0
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent negative control

Amount / concentration applied:

0.1 mL

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: slit lamp

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.7

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.7

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.7

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3.7

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3.7

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 13 days

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 13 days

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 13 days

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Executive summary:

This study was conducted to evaluate the potential eye irritation/corrosion after a single application of the test substance, 2,2’-[ethylenebis(oxymethylene)]bisoxirane, in three 11 -week-old male New Zealand White rabbits.

0.1 mL of the test substance (100% test substance) was instilled to the conjunctivae sac of the right eye of one animal after gently pulling over the lower eyelid away from the eyeball.

The response scores of the cornea, iris and conjunctivae were recorded according to the method of Draize. In the initial and confirmatory tests, eye irritations were observed at 72 h after test substance application; therefore, additional eye observations were continued up to Day 21. Corneal opacity, redness of the conjunctivae and chemosis of the conjunctivae were observed in all animals until Day 21.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin corrosion/irritation potential was evaluated in an in vivo test with New Zealand White rabbits. The mean value for erythema/eschar and oedema at 24, 48 and 72 h was respectively 1.7 and 0 in all 3 tested animals. The observed effects appeared to be reversible. Therefore the substance should not be classified for skin corrosion/irritation.

The eye damage/irritation potential was evaluated in an in vivo test with New Zealand White rabbits. The observed effects at the cornea and conjunctivae were not reversible after 21 days in all 3 tested animals. Therefore the substance should be classified Eye Dam. 1.