1H-Indole-6-carboxylic acid, 1-(2-chloroacetyl)-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 423) 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)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

PD 283 XX

IUPAC Name:

PD 283 XX

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): PD 283 XX
- Physical state: yellow powder
- Analytical purity: 97.6 % (HPLC)
- Analysis test date: 12 january 2006
- Purity to be retested: january 2007
- Lot/batch No.: V12TFA00072
- Storage condition of test material: 20°C

Test animals

Species:

rat

Strain:

other: Crl:WI (Han), SPF quality

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, via Biological Laboratory Services, Boehringer Ingelheim
- Age at study initiation: approximately 7 weeks
- Weight at study initiation: males 148 g to 157 g, females 126 g to 137 g
- Fasting period before study: Prior to administration, the rats were kept over night without food
- Housing:
- Diet (e.g. ad libitum): pelleted dry food, ad libitum
- Water (e.g. ad libitum): Municipal tap drinking water, ad libitum
- Acclimation period: 5- to 7-days

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

Doses:

200, 2000 mg/kg

No. of animals per sex per dose:

3 femals / 200 mg/kg
3 males/ 3 femals 2000 mg/kg

Control animals:

no

Details on study design:

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

Results and discussion

Preliminary study:

JUSTIFICATION OF DOSE LEVELS:
In the absence of prior experience, 200 mg/kg body weight was chosen as the initial dose.
The second dose was selected based on the animals’ response to 200 mg/kg.

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 and 2000 mg/kg, respectively, as well as in one male at the latter dose.
Following 2000 mg/kg, necropsy of two males revealed disseminated, dark red discolorations up to the size of a pin tip on the surface 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 PD 283 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 PD 283 XX, is set above 2000 mg/kg for male and female rats.