1H-Indole-6-carboxylic acid, 2,3-dihydro-3-(methoxyphenylmethylene)-2-oxo-, methyl ester, (3E)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2 February - 23 February 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD ) and in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

throughout the entire study period, the room temperature was slightly below 20 °C

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

CD 352 XX

IUPAC Name:

CD 352 XX

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): CD 352 XX
- Physical state: yellow crystals
- Analytical purity: 99.9 area % (HPLC)
- Purity test date: 12 january 2006
- Lot/batch No.: V12CRE00175
- Expiration date of the lot/batch: until november 2006
- Storage condition of test material: at room temperature, protected from light

Test animals

Species:

rat

Strain:

other: Crl:WI (Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services Germany GmbH, Sulzfeld, Germany
via Biological Laboratory Services, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach/Riss, Germany
- Age at study initiation: approximately 7 weeks
- Weight at study initiation: males 155 g to 164 g, females 123 g to 139 g
- Fasting period before study: over night
- Housing: barrier-protected system under standardized air conditions
- Diet (e.g. ad libitum): dry food ad libitum,
- Water (e.g. ad libitum): Municipal tap drinking water ad libitum
- Acclimation period: 5- to 7-day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 45% - 75%
- Air changes (per hr): minimum of 10 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12 hours

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5% aqueous hydroxyethylcellulose

Details on oral exposure:

VEHICLE

- Amount of vehicle (if gavage): 20 mL/kg

Doses:

200, 2000 mg/kg

No. of animals per sex per dose:

200 mg/kg: 3 females rats
2000 mg/kg: 3 males and 3 female rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: twice a day working days, once at non working days
- Necropsy of survivors performed: yes
- Other examinations performed: body weight

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

other: ALD (approximate lethal dose)

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed subsequent to a single oral administration of 200 mg/kg and 2000 mg/kg, respectively.

Clinical signs:

other: Piloerection was observed at both doses as the only clinical sign on day 1

Gross pathology:

No necropsy findings were noted in females treated with 200 mg/kg or 2000 mg/kg. Following 2000 mg/kg no alterations were observed in two male rats and one male rat revealed multiple disseminated, pin-sized, dark red discolourations of the lungs.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, which was designed to evaluate in rats the acute
toxicity of CD 352 XX subsequent to a single oral administration by gavage, no mortality
was seen subsequent to oral administration of 200 mg/kg and 2000 mg/kg, respectively.
Thus, the approximate lethal dose (ALD) for CD 352 XX is set above 2000 mg/kg for male and female rats.