1H-Indole-6-carboxylic acid, 2,3-dihydro-2-oxo-, methyl ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 Jan - 19 Feb 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

methyl 2-oxo-2,3-dihydro-1H-indole-6-carboxylate

EC Number:

604-263-8

Cas Number:

14192-26-8

Molecular formula:

C10 H9 N O3

IUPAC Name:

methyl 2-oxo-2,3-dihydro-1H-indole-6-carboxylate

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

other: CrlGlxBrlHan: WI (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Germany
- Age at study initiation: 8 weeks
- Weight at study initiation: Males: 188-192 g, females: 138-148 g
- Fasting period before study:
- Housing: Noryl cages, type IV
- Diet (e.g. ad libitum): ad libitum in pellet form (NAF AG 9433 certified dry diet, Eberle Nafag AG, Gossau/Switzerland)
- Water (e.g. ad libitum): Municipal drinking water was available at any time via drinking bottles.
- Acclimation period: 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20± 3°C
- Humidity (%): 45-75%
- Air changes (per hr): maximum 12xlh
- Photoperiod (hrs dark / hrs light): 12/12 hours

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: suspended in 0,5% Natrosol 250 HX

Details on oral exposure:

The test substance was suspended in 0.5% Natrosol250 HX (Hydroxyethylcellulose) to achieve an administration volume of 20 mL/kg. The administered volume, based on the individual body weight of the animals determined on the day of administration, was given by gavage to fasted animals.

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 male and 3 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
The overall appearance and behavior of each animal was observed at least twice a day. On weekends and non-working days, clinical observations
were performed in the moming only.
Body weight of the animals was determined on the day of administration ( day 1 ), as well as on days 2, 8 and 15 of the experiment
- Necropsy of survivors performed: yes

Statistics:

The data were analyzed by validated SAS based statistic programs. These were integrated in the BI02100 Reporting System. The statistical results
were reported in standardized lists.
Validated templates were used for the statistical analysis and reporting.
In summary or overview lists descriptive statistics are reported (sample size = n, arithmetic mean = mv and standard deviation = sd).

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

other: ALD

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed

Clinical signs:

other: No clinical signs were observed

Body weight:

other body weight observations

Remarks:

Normal body weight gain

Gross pathology:

At necropsy of the animals, no gross pathologic findings were observed.

Applicant's summary and conclusion

Interpretation of results:

other: not classified acc. CLP

Conclusions:

According to the results of the present study, the ALD (approximate Iethal dose) for BIBF 1120 Indol in rats following single oral administration is above 2000 mg/kg.