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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

Adopted: 24 February 1987

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

218-746-2

EC Name:

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

Cas Number:

2224-15-9

Molecular formula:

C8H14O4

IUPAC Name:

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

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ORIENTBIO INC., Republic of Korea
- Age at study initiation: males: 8 weeks old, females: 9 weeks old
- Weight at study initiation: males: 277.1−304.1 g, females: 222.2−240.9 g
- Housing: Stainless wire mesh cage, 260W×350D×210H (mm); 1 animal/cage (during the study)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: all animals were quarantined for 3 days, moved from the quarantine room to the animal room and acclimated for 4 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): measurement value: 20.6−24.5°C, permissible range: 19.0−25.0°C
- Humidity (%): Measurement value: 44.1−55.3%, permissible range: 30.0−70.0%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 4 x 5 cm

REMOVAL OF TEST SUBSTANCE
- Washing: the lint tape, plastic film, Soft Cloth Tape with Liner and surgical tape were removed and any residual test substance was removed using absorbent cotton moistened with tepid water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 1.74 mL/kg at 2000 mg/kg (density taken into account)

Duration of exposure:

24 h

Doses:

0 and 2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

yes

Results and discussion

Preliminary study:

In a preliminary study, one male and one female rat were dermally dosed at a dose of 2,000 mg/kg or 1.74 mL/kg. No deaths occurred. Therefore, the dose level was selected at 2,000 mg/kg for this study.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths in the 2000 mg/kg group

Clinical signs:

other: No abnormalities of clinical signs were in any animal in the control group and 2,000 mg/kg group throughout the study. However, erythema, edema, exfoliation and/or crust formation were observed in the application sites of test substance in males and femal

Gross pathology:

At necropsy, crust was observed in the application site one male animal in the 2,000 mg/kg group.

Other findings:

- Histopathology: At necropsy, crust was observed in the application site one male animal in the 2,000 mg/kg group. Slight inflammation with neutrophil/cell debris/bacteria colony was observed in concordance with the crust in the application site. This microscopic finding was considered to be a test substance-related change in terms of clinical sign.

Applicant's summary and conclusion

Executive summary:

The purpose of this study was to assess the potential toxicity and the approximate LD50 value of the test substance, 2,2’-[ethylenebis(oxymethylene)]bisoxirane, following a single dermal application to Sprague-Dawley rats.

Test groups consisted of one dose group at a dose of 2,000 mg/kg and a control group, and each group consisted of 5 males and 5 females. All animals were monitored for clinical signs and body weight changes during the 14-day observation period. They were subjected to gross necropsy at the end of the observation period.

There were no deaths of animals in the 2,000 mg/kg groups. No test substance-related effects were observed in clinical signs, body weight data or necropsy findings in the 2,000 mg/kg groups. However, erythema, edema, exfoliation and/or crust formation were observed in the application sites of test substance in males and females from Day 1 to Day 14 after dosing.

Based on the result of this study, the LD50 value of the test substance, 2,2’-[ethylenebis (oxymethylene)]bisoxirane, was considered to be greater than 2,000 mg/kg in male and female rats under the conditions of this study.