Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22 August - 12 October 2005
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:
2006
Report date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
IN 78281
IUPAC Name:
IN 78281
Details on test material:
- Name of test material (as cited in study report): IN00078281 (IN 78281)
- Physical state: White powder
- Analytical purity: The Certificate of Analysis was provided to the Study Director
- Purity test date:
- Lot/batch No.: 7889-058-10 (Exp. Dec 2006)
- Expiration date of the lot/batch:
- Supplier: Boehringer Ingelheim Pharmaceuticals
- Stability under test conditions: Stability data on bulk test material was not provided to the Study Director
- Storage condition of test material: Room Temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: 9-11 weeks
- Weight at study initiation: 176-290 grams
- Fasting period before study: overnight
- Housing: Animals were group housed by sex upon receipt and individually housed upon assignment to study
- Diet (e.g. ad libitum): ad libitum, Harlan Teklad Rodent Diet (certified)
- Water (e.g. ad libitum): ad libitum, tap water
- Acclimation period: minimum 5 days prior dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23°C
- Humidity (%): 27 to 72%
- Air changes (per hr): The room in which the animals were kept was documented in the study records.
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5 % hydroxyethylcellulose in deionized water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 ml/kg
Doses:
300, 2000 mg/kg bw
No. of animals per sex per dose:
12; three male and three female animals per dose were used
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were performed at approximately 30 minutes, 1 and 4 hours (+-15 minutes) after dosing and once daily through day 15. Signs of toxicity were recorded as they are observed including the time of onset, degree and duration. Body weights were measured on Days 1 (fasted), 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: mortality daily
Statistics:
None performed

Results and discussion

Preliminary study:
All animals received for this study were assessed as to their general health by a member of the veterinary staff or other authorized personnel. During the acclimation period, each rat was observed at least once daily for any abnormalities or for the development of infectious disease. Only animals that were determined suitable for use were assigned to this study.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 300 - <= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No moratily was observed in the animals at 300 or 2000 mg/kg.
Clinical signs:
other: No clinical signs observed in the animals at 300 or 2000 mg/kg.
Gross pathology:
No visible lesions were observed in any of the animals at 300 or 2000 mg/kg at terminal necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item administered orally at a dose level of 2000 mg/kg body weight in male and female rats was considered to be a Category 5 test substance with an LD50 greater than 2000-5000 mg/kg.