2-isopropyl-N-hydroxyethyl 1,3-oxazolidine;methyl carbonato-N-ethyl-2-isopropyl-1,3-oxazolidine;reaction mass of: carbonato-bis-N-ethyl-2-isopropyl-1,3-oxazolidine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 1998-02-12 to 1998-04-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

cited as: Directive 92/69/EEC method B1 bis, from 29 Dec 1992

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

adopted: 17 Jul 1992

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

429-990-6

EC Name:

-

Molecular formula:

Not applicable as multi-const. substance. Please refer to IUCLID section 1.2 for details on constituents.

IUPAC Name:

2-[(2R)-2-(propan-2-yl)-1,3-oxazolidin-3-yl]ethan-1-ol; 2-[(2R)-2-(propan-2-yl)-1,3-oxazolidin-3-yl]ethyl 2-[(2S)-2-(propan-2-yl)-1,3-oxazolidin-3-yl]ethyl carbonate; 2-[(2S)-2-(propan-2-yl)-1,3-oxazolidin-3-yl]ethan-1-ol; bis{2-[(2S)-2-(propan-2-yl)-1,3-oxazolidin-3-yl]ethyl} carbonate; methyl 2-[(2R)-2-(propan-2-yl)-1,3-oxazolidin-3-yl]ethyl carbonate; methyl 2-[(2S)-2-(propan-2-yl)-1,3-oxazolidin-3-yl]ethyl carbonate

Test material form:

liquid: viscous

Test animals

Species:

rat

Strain:

other: Hsd. Brl:WH

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester
- Age at study initiation: five to eight weeks old
- Weight at study initiation: 145 to 159 g (males); 129 to 143 g (females)
- Fasting period before study: yes; from the evening prior to dosing until approximately three hours after dosing
- Housing: stainless steel mesh cages (minimum internal dimensions of 55 x 34 x 20 cm)
- Diet: ad libitum; SQC(E) Rat and Mouse Maintenance Diet No 1. from Special Diets Services Ltd. Witham
- Water: tab water ad libitum
- Acclimation period: 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 40 to 80 %
- Air changes: 10 air changes per hour
- Photoperiod: 12 hours light from 6.00 a.m. to 6.00 p.m.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

Desiccated corn oil

Details on oral exposure:

VEHICLE
Dose levels were expressed gravimetrically and in terms of test article received. The test article was dispersed in desiccated com oil. The formulated concentrations were calculated from the selected dose level and dose volume (10 mL/kg). All formulations were used on the day of preparation.

MAXIMUM DOSE VOLUME APPLIED:
Individual dose volumes (mL) were calculated from the fasted body weights of the rats on the morning of dosing (Day 1) and the selected dose volume (10 mL/kg). Each rat was dosed once on Day 1 by passing the tip of a catheter along the oesophagus and instilling the test article into the gastric lumen. Doses were administered using plastic syringes and rubber catheters.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 male and female rats per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Treated rats were observed closely for clinical signs of reaction to treatment. Clinical signs were recorded frequently on Day 1 and regularly for the remainder of the study, (the minimum schedule being at least once within half an hour of dosing and four times within the first four hours following administration, twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period). Individual records of clinical signs were maintained for each treated rat. Rats were weighed on Day -1 (day before dosing), Day 1, Day 8 and Day 15.
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:

The preliminary investigation was conducted using two groups of two female fasted rats dosed at 500 and 2000 mg/kg. There were no deaths among pairs of female fasted rats following a single oral administration of Ineozol LV at either 500 or 2000 mg/kg. Thus, the main test was performed with a dose level of 2000 mg/kg bw.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: There were no treatment related signs of toxicity following administration of the test substance.

Gross pathology:

Necropsy revealed no macroscopic changes in nine rats. One eye of a single rat was found to be distended. In the absence of corroborative in-*life observations this finding was discounted as a toxic effect of the test article.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Single oral administration of Incozol LV at a dose level of 2000 mg/kg bw caused no deaths in a group of ten fasted rats. Accordingly, the acute minimum lethal oral dose of Incozol LV to rats was found to be greater than 2000 mg/kg bw. The discriminating dose was found to be 2000 mg/kg bw.

Executive summary:

A study was conducted according to OECD TG 420 and Directive 92/69/EEC method B1 bis to determine the acute toxicity of Incozol LV by oral gavage to rat. Therefore a preliminary test with 2 female rats at dose of 500 and 2000 mg/kg bw was performed. There were no deaths among pairs of female fasted rats following a single oral administration of Ineozol LV at either 500 or 2000 mg/kg bw. Thus, the main study was performed with 5 male and 5 female rats at 500 or 2000 mg/kg bw. The test item was dispersed in desiccated corn oil and administered at a dose volume of 10 mL/kg on Day 1. All animals were killed on Day 15 and subsequently underwent a full necropsy. No mortality was observed and there were no overt signs of reaction to treatment. All rats achieved body weight gains during the first and second weeks of the study. Necropsy revealed no macroscopic changes in nine rats. One eye of a single rat was found to be distended. In the absence of corroborative in-life observations this finding was discounted as a toxic effect of the test article. Single oral administration of Incozol LV at a dose level of 2000 mg/kg bw caused no deaths in a group of ten fasted rats. Accordingly, the acute minimum lethal oral dose of Incozol LV to rats was found to be greater than 2000 mg/kg bw. The discriminating dose was found to be 2000 mg/kg bw.