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

Acute Toxicity: oral

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(adopted 17 Dec 2001)

Deviations:

no

Test guideline 2

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

adopted Dec 2002

Deviations:

no

Test guideline 4

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

Test material

Test material information

Constituent 1

Reference substance name:

3-ethenyl-5-methyl-1,3-oxazolidin-2-one

EC Number:

809-852-5

Cas Number:

3395-98-0

Molecular formula:

C6H9NO2

IUPAC Name:

3-ethenyl-5-methyl-1,3-oxazolidin-2-one

Details on test material:

- Name of test material (as cited in study report): 5-Methyl-3-vinyloxazolidin-2-on
- Physical state: liquid / colorless to yellowish
- Test item No.: 14/0031-2
- Lot/batch No.: DEIMLIB 2014/2
- Analytical purity: 98.7 corr. area %
- Stability under test conditions: The stability of the test item under storage conditions over the test period was guaranteed by the sponsor.
- Storage condition of test material: Room temperature
- Expire date: October 01, 2014

Test animals

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

Administration / exposure

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.

Results and discussion

Effect levels

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).

Applicant's summary and conclusion

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