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

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

Adopted: 17 December 2001

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ORIENTBIO INC., Republic of Korea
- Age at study initiation: 8−9 weeks old
- Weight at study initiation: 180.8−213.8 g
- Fasting period before study: Animals were fasted overnight, approximately 16 hours prior to dosing. Feed was provided approximately 4 hours post dosing.
- Housing: one animal/cage
- 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: 20.6−24.2 (permissible range: 19.0-25.0)
- Humidity (%): measurement value: 39.9−54.2 (permissible range: 30.0-70.0)
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

water for injection

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Amount of vehicle (if gavage): individual doses were calculated based on the animal’s body weight recorded just prior to dosing at a dose volume of 10 mL/kg body weight.
- Lot/batch no.: DBA6008 (JW Pharmaceutical Co., Ltd., Republic of Korea)

CLASS METHOD
- Rationale for the selection of the starting dose: Due to the low expected toxicity of the test substance, 2,000 mg/kg was selected as the starting dose for this study based on the information supplied by the sponsor.

Doses:

300 and 2000 mg/kg

No. of animals per sex per dose:

300 mg/kg: 6 animals
2000 mg/kg: 3 animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
All animals were observed for mortality, general condition and clinical signs (type, severity, time of onset and recovery) at 30 minutes after dosing and at 1, 2, 4 and 6 hours after dosing on Day 0 and once daily thereafter for 14 days (Day 1−Day 14).
The body weight was recorded prior to dosing on Day 0, on Days 1, 3, 7 and on the day of necropsy (Day 14).
- Necropsy of survivors performed: yes
- Other examinations performed: Since no gross findings were observed at necropsy, histopathological examinations were not performed.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

300 mg/kg: 0/6 deaths
2000 mg/kg: 3/3 deaths

Clinical signs:

other: In all three dead animals at 2,000 mg/kg, abnormal gait and/or lacrimation were observed at 2 and 4 hours after dosing.

Gross pathology:

No grossly visible findings were observed in any animal at 300 and 2,000 mg/kg.

Interpretation of results:

Category 4 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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

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

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

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

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

In an acute oral toxicity test with rats the LD50 was found to be between 300 and 2000 mg/kg. This corresponds with a classification Acute Tox. 4. via the oral route.

In an acute dermal toxicity test with rats no animals died at the highest dose of 2000 mg/kg. Therefore no classification is warranted for acute toxicity via the dermal route.