2-Oxazolidinone, 3-ethenyl-5-methyl-

Endpoint summary

Description of key information

LD50 oral: >300 - < 2000 mg/kg
LD50 dermal: > 2000 mg/kg

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

Study period:

2014-05-20 - 2014-06-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline Study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

(adopted 17 Dec 2001)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

(adopted 30 May 2008)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

adopted Dec 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nosan No. 8147

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Landesanstalt für Umwelt, Messungen und Naturschutz Baden-Württemberg

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Age at study initiation: 8 - 12 weeks (nulliparous, non-pregnant females)
- Weight at study initiation: 183 - 190 g
- Housing: single housing in Makrolon cage, type III
- Diet: VRF1 (P); SDS Special Diets Services, 67122 Altrip, Germany
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 15 g /100 mL
- Amount of vehicle (if gavage): 2 mL/kg bw


MAXIMUM DOSE VOLUME APPLIED: 2 mL/kg bw

CLASS METHOD (if applicable)
- By request of the sponsor a starting dose of 2000 mg/kg bw was chosen in the first step with 3 female animals.
As all animals died, 300 mg/kg bw were administered to 3 female rats in the second step. Because no mortality occurred, 300 mg/kg bw were
administered to another group of 3 female animals in the third step.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

Group 1 (300 mg/kg): 3 females
Group 2 (300 mg/kg) : 3 females
Group 3 (2000 mg/kg undiluted): 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the day of death
or sacrifice moribung starting with study day 1.
Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals.
- Necropsy of survivors performed: Necropsy with gross-pathology examination was performed on the last day of the observation period after
sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations. Necropsy of all animals that died as early as possible after death.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Two animals of the 2000 mg/kg test group were found dead at hour 4. One animal of this test group was sacrificed in a moribund state at hour 5.
No mortality occurred in both 300 mg/kg bw test groups.

Clinical signs:

other: All animals of the 2000 mg/kg bw test group showed poor general state, dyspnea, apathy and abdominal position from hour 0 until hour 3 or hour 4. In two animals atonia was noted from hour 0 until hour 3 and in the third animal from hour 1 until hour 2. I

Gross pathology:

The following macroscopic pathologic findings were observed in the animals that died or in the single moribund sacrificed animal in the 2000 mg/kg bw test group (3 females): Yellowish discoloration of the stomach contents, red discoloration of the glandular stomach and red discoloration of the small intestine. There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period (300 mg/kg bw: 6 females).

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the median lethal dose of 5-Methyl-3-vinyloxazolidin-2-on after oral administration was found to be greater than 300 mg/kg bw and less than 2000 mg/kg bw in rats.

Executive summary:

In an acute oral toxicity study performed according to the Acute Toxic Class method, doses of 2000 and 300 mg/kg bw of the test item 5-Methyl-3-vinyloxazolidin-2-on (undiluted or preparations in corn oil Ph.Eur.) were administered by gavage to three test groups of three fasted Wistar rats each (2000 mg/kg bw in 3 females, 300 mg/kg bw in 6 females).

The following test substance-related clinical observations were recorded, clinical signs occurred within one day after administration:

2000 mg/kg (single test group):

Mortality in all animals (two animals died, one animal was sacrificed in a moribund state). Poor general state, Dyspnea, Apathy, Atonia and Abdominal position in all animals

Macroscopic pathological findings in the animals that died/ that was sacrificed moribund:

Yellowish discoloration of the stomach contents. Red discoloration of the glandular stomach. Red discoloration of the small intestine.

300 mg/kg (first and second test group):

No mortality occurred. Impaired general state, Piloerectio and Cowering posiotion in all animals. Dyspnea in all animals in the first test group. Abdominal position in one animal in the second test group.

The mean body weight of the animals increased within the normal range throughout the study period.

There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period.

The acute oral LD50 was calculated to be: LD50, oral, rat >300 < 2000 mg/kg bw

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

Study period:

2014-07-23 - 2014-08-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline Study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

(adopted 30 May 2008)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

(adopted Aug 1998)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: - Japan MAFF Testing Guideline of 12 Nosan No. 8147 402.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Landesanstalt für Umwelt, Messungen und Naturschutz Baden-Württemberg

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks nulliparous and non-pregnant
- Weight at study initiation: males: 226-239 g, females:203-220 g
- Housing: single housing in Makrolon cage, type III
- Diet: VRF1 (P); SDS Special Diets Services, 67122 Altrip, Germany
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: about 40 cm² clipped skin of the dorsal and dorsolateral parts of the trunk
- % coverage: at least 10% of the body surface
- Type of wrap if used: The test item was covered with an air-permeable dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.82 mL/ kg

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weight shortly before administration (day 0), weekly thereafter and on the last day of observation. Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals.
- Necropsy of survivors performed: yes
- Scoring of skin findings: Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), weekly therafter and on the last day of observation. Scoring was performed according to Draize.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred within the study period.

Clinical signs:

other: No systemic clinical signs were observed during clinical examination within the study period. No local effects were observed.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the median lethal dose (LD50) of 5-Methyl-3-vinyloxazolidin after dermal application was found to be greater than 2000 mg/kg bw in male and female rats.

Executive summary:

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of 5-Methyl-3-vinyloxazolidin-2-on (undiluted) to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days.

Neither mortality, nor signs of systemic toxicity or skin effects were observed in the animals.

No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.

The mean body weight of the male animals increased within the normal range throughout the study period. In the female group three females marginally lost weight and another animal did not gain weight during the first week, but body weights were within the normal range during the second week. In the remaining fifth female the body weight increased within the normal range throughout the study period.

This effect is observed at times in the rat strain used, because in the required age range the female animals have already reached the phase of slow growth. Due to the fact that stagnation of body weight is commonly known for females dermally applied, this stagnation is considered to be unspecific.

No mortality occurred. Accordingly, the acute dermal median lethal dose (LD50) was determined to be

LD50, dermal, rat > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

In an acute oral toxicity study performed according to the Acute Toxic Class method (OECD 423; BASF SE 2014), doses of 2000 and 300 mg/kg bw of 5-Methyl-3-vinyloxazolidin-2-on (undiluted or preparations in corn oil Ph.Eur.) were administered by gavage to three test groups of three fasted Wistar rats each (2000 mg/kg bw in 3 females, 300 mg/kg bw in 6 females). The following test substance-related clinical observations were recorded, clinical signs occurred within one day after administration:

2000 mg/kg (single test group):

Mortality in all animals (two animals died, one animal was sacrificed in a moribund state). Poor general state, Dyspnea, Apathy, Atonia and Abdominal position in all animals

Macroscopic pathological findings in the animals that died/ that was sacrificed moribund:

Yellowish discoloration of the stomach contents. Red discoloration of the glandular stomach. Red discoloration of the small intestine.

300 mg/kg (first and second test group):

No mortality occurred. Impaired general state, Piloerectio and Cowering posiotion in all animals. Dyspnea in all animals in the first test group. Abdominal position in one animal in the second test group.

The mean body weight of the animals increased within the normal range throughout the study period.

There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period.

The acute oral LD50 was calculated to be >300 < 2000 mg/kg bw.

In an acute dermal toxicity study (Limit Test; BASF SE 2014), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of 5-Methyl-3-vinyloxazolidin-2-on (undiluted) to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. Neither mortality, nor signs of systemic toxicity or skin effects were observed in the animals. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. The mean body weight of the male animals increased within the normal range throughout the study period. In the female group three females marginally lost weight and another animal did not gain weight during the first week, but body weights were within the normal range during the second week. In the remaining fifth female the body weight increased within the normal range throughout the study period. No mortality occurred. Accordingly, the acute dermal median lethal dose (LD50) was determined to be > 2000 mg/kg bw.

Justification for classification or non-classification

5 -Methyl-3 -vinyl-1,3 -oxazolidin-2 -one is harmful after oral administration (cat. 4, H302) according to the criteria of EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008.