4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl)-N-(2-ethyl-3-oxo-1,2-oxazolidin-4-yl)-2-methylbenzamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

8 Mar 2016 to 5 Apr 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Version / remarks:

2018

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl)-N-(2-ethyl-3-oxo-1,2-oxazolidin-4-yl)-2-methylbenzamide

Cas Number:

2061933-85-3

Molecular formula:

C23H19Cl2F4N3O4

IUPAC Name:

4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl)-N-(2-ethyl-3-oxo-1,2-oxazolidin-4-yl)-2-methylbenzamide

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:(WI)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sex: Female rat, nulliparous and non-pregnant
- Age: Young adult rats, 8 weeks old
- Body weight when treated: 199 – 216 g
- Fasting period: animals were fasted overnight prior to treatment and food was returned approximately 3 hours after dosing
- Diet: Animals received "Autoclavable complete diet for rats and mice – breeding and maintenance" ad libitum
- Water: Tap water from municipal supply, provided in 500 mL bottles ad libitum
- Housing: Individual caging Type II. polypropylene/polycarbonate cages. Laboratory bedding were available to animals during the study
- Acclimatisation period: At least 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.0 – 21.9
- Humidity (%): 26 – 70
- Air changes (exchanges/hour): 15 - 20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: from 08 Mar 2016 to 05 Apr 2016

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5 % (w/v) carboxymethyl cellulose and 0.1 % (v/v) Tween 80

Details on oral exposure:

The applied dose volume was 10 mL/kg bw

Doses:

Starting dose of 1750 mg/kg bw, then 5000 mg/kg bw as no clinical signs or lethality were observed, followed by a 14 day observation period. Animals were treated with a single oral (gavage) dose.

No. of animals per sex per dose:

4

Control animals:

no

Details on study design:

All animals were observed individually after dosing at 30 minutes, then 1, 2, 3, 4, and 6 hours after dosing and once each day for 14 days thereafter. Individual observations were performed on the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. The body weights were recorded on Days -1, 0 (before treatment), 7 and 14. All animals were euthanised at the end of the observation period by exsanguination under pentobarbital anaesthesia and all animals were subjected to macroscopic examination. After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs were observed. All gross pathological changes were recorded for each animal on the post mortem record sheets and the animals were discarded.

Statistics:

The oral LD50 was calculated using the statistical programme (AOT 425 Stat Pgm) version: 1.0, 2001, used for the selection of dose levels and calculation of the LD50 values.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

other: No clinical signs were observed during the observation period.

Gross pathology:

At necropsy, there were no observations to be reported at a dose level of 1750 and 5000 mg/kg bw.

Any other information on results incl. tables

Table 1: Acute oral toxicity of the test substance in rats, application scheme and mortality data

Animal Number	Dose [mg/kg body weight]	Volume Dosed [mL]	Bodyweight [g]	Mortality
1	1750	2.1	207	Survived
2	5000	2.0	199	Survived
3	5000	2.0	199	Survived
4	5000	2.2	216	Survived

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute oral median lethal dose (LD50) of the test substance was greater than 5000 mg/kg bw in female Crl:WI rats.

Executive summary:

An acute oral toxicity study (OECD 425, GLP compliant) (up and down procedure) was conducted with 4 female Crl:WI rats. Animals were treated with a single oral (gavage) dose of the test substance, at a dose level of 1750 or 5000 mg/kg body weight (bw) followed by a 14 day observation period. The animals were fasted overnight prior to treatment and food was returned 3 hours after dosing. Animals were observed individually after dosing at 30 minutes, then at 1, 2, 3, 4 and 6 hours post treatment and once each day for 14 days, thereafter. Body weight was measured on Day -1, just before dosing and weekly thereafter. All animals were examined macroscopically at the end of the observation period.  There was no mortality during the study. No clinical signs were observed during the observation period. There were no treatment related effects on body weight or body weight gain. Body weights were within the range commonly recorded for this strain and age. At necropsy, there were no observations to be reported at a dose level of 1750 and 5000 mg/kg bw.

Under the conditions of this study, the acute oral median lethal dose (LD50) of the test substance, the test substance, was greater than 5000 mg/kg bw in female Crl:WI rats.