4-[(2E)-3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-2-enoyl]-N-[(4R)-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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008

Deviations:

no

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-[3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-2-enoyl]-N-(2-ethyl-3-oxo-1,2-oxazolidin-4-yl)-2-methylbenzamide

Molecular formula:

C23H18Cl2F4N2O4

IUPAC Name:

4-[3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-2-enoyl]-N-(2-ethyl-3-oxo-1,2-oxazolidin-4-yl)-2-methylbenzamide

Test material form:

solid

Details on test material:

Off-white

Test animals

Species:

rat

Strain:

other: Crl:WI

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 9-10 weeks old
- Weight at study initiation: 187 - 212 g
- Fasting period before study: overnight
- Housing: individually in Type II polypropylene/polycarbonate cages with deep wood sawdust bedding
- Diet: ssniff SM R/M autoclavable complete diet for rats ad libitum (ssniff Spezialdiäten GmbH, D-59494 Soest, Germany)
- Water: tap water from municipal supply from 500 mL bottles ad libitum
- Acclimation period: at least 18 days prior to test
- Method of randomisation in assigning animals to test and control groups: selected randomly by hand at time of delivery

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12 hours light (from 6.00 am to 6.00 pm)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

The substance was formulated on the day of dosing at a concentration of 200 mg/mL in 0.5% carboxymethyl cellulose in distilled water. The dose volume was 10 mL/kg bw.

Doses:

Starting dose was 2000 mg/kg bw

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: treated animals were observed individually 30 minutes after dosing, then at 1, 2, 3, 4 and 6 hours after treatment, and then daily for the observation period. Body weight was measured before the test, on day 7 and on day 14.
- Necropsy of survivors performed: yes
- Clinical signs including body weight: observation of skin and fur, eys, mucous membranes, respiratory, circulatory and central nervous system, somatomotor activity and behavioural pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

other: Slight decrease in activity in one animal, hunched back in one animal.

Gross pathology:

No abnormal findings.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

After a single oral administration by gavage, the oral LD50 was found to be >2000 mg/kg in female rats.

Executive summary:

The acute oral toxicity of the substance was tested under GLP to OECD TG 425 (up and down procedure). The study was conducted with five female Crl:WI rats, receiving a single oral dose by gavage of 2000 mg/kg bw formulated in 10 mL of 0.5% carboxymethyl cellulose. Animals were observed intensively in the first hours after treatment and then daily for a period of 14 days for clinical signs. Body weight was determined at the start of the test, and on day 7 and day 14 of the observation period. Treatment caused slighlty decreased activity in one animal and hunched back in one animal. All symptoms had disappeared after six hours after treatment. Normal body weight gain was observed. No abnormal findings were seen during necropsy following the observation period. The oral LD50 in female rats was found to be >2000 mg/kg bw in this study.