ethyl 6-(3-chloro-2-fluorobenzyl)-1-[(2S)-1-hydroxy-3-methylbutan-2-yl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26/07/2010-19/08/2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: Commission regulation 440/2008, L142, Annex Part B

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: EPA OPPTS 870.1000 (Acute Toxicity testing background)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

ethyl 6-(3-chloro-2-fluorobenzyl)-1-[(2S)-1-hydroxy-3-methylbutan-2-yl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate

EC Number:

638-800-2

Cas Number:

949465-91-2

Molecular formula:

C25H27ClFNO5

IUPAC Name:

ethyl 6-(3-chloro-2-fluorobenzyl)-1-[(2S)-1-hydroxy-3-methylbutan-2-yl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate

Test material form:

solid: crystalline

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

The animals were derived from a controlled full-barrier maintained breeding system (SPF). According to Art. 9.2, No.7 of the German Act on Animal Welfare the animals were bred for experimental purposes.
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-9 weeks old
- Weight at study initiation: Animals N. 1-3, step 1: 153-180 g; Animals N. 4-6, step 2: 152-170 g
- Housing: Full-barrier in an air-conditioned room
- Diet (e.g. ad libitum): free access
- Water (e.g. ad libitum): free access
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 55+/- 10%
- Air changes (per hr): 10 x/ hour
- Photoperiod (hrs dark / hrs light): Artificial light, 12/ 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

cotton seed oil

Doses:

2000 mg/kg bw
The test item was suspended in a veichel (Cottonseed oil) at a concentration of 0.4 g/ml and administered at a dose V of 5 mL/kg.

No. of animals per sex per dose:

3 per step/ 2 steps performed

Control animals:

yes

Details on study design:

All animals were observed for 14 days after dosing for general clinical signs, morbidity and mortality.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived until the end of the study without showing any signs of toxicity.

Clinical signs:

No signs of toxicology.

Body weight:

None of the animals showed weight loss during the observation period.

Gross pathology:

The test item showed no acute oral toxicity characteristics after a single dose administration.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the present study, single oral application of the test item GS-9205 to rats at a dose of 2000 mg/kg bw was associated with no signs of toxicity or mortality.
The LD50 after a single oral administration to female rats, observed over a period of 14 days is >2000 mg/kg bw.
According to Annex I of Reg 1272/2008 EC the test item is not classified.