Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented and reported study, conducted according to internationally accepted technical guidelines and in compliance with GLP in recognized contract research organization. Fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
of 1996
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
of 1996
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Wistar rats, strain: Crl:(WI) BR (outbred, SPF-Quality) with appropriate range of bodyweight at study start.
Females were nulliparous and non-pregnant.
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation (day of dosing): Approx. 7 weeks.
- Weight at study initiation (day of dosing): Males: mean: 255 g, minimum 252 g, maximum 260 g
Females: mean: 177 g, minimum 170 g, maximum 181 g.
- Fasting period: Overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours post administration.
Water was available.
- Housing: Group housing with 3 animals/Macrolon type IV cage.
- Diet (ad libitum): Commercially available standard pelleted laboratory animal diet (from Altromin, code VRF 1).
- Water (ad libitum): Tap water
- Acclimation period: At least 5 days before start of dosing under laboratory conditions.


ENVIRONMENTAL CONDITIONS

Animals were housed in a controlled environment with optimal conditions considered to be approximately 15 air changes per hour, 21±3°C, 30-70% relative humidity, and 12 hours artificial fluorescent light and 12 hours darkness per day.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
DOSE VOLUME APPLIED:

A dose volume of 1.68 mL unchanged test substance per kg bodyweight was administered by oral gavage. In view of a specific gravity of 1.19, the administered dose volume corresponds to a dose of 2000 mg unchanged test substance per kg body weight.

CLASS METHOD - Rationale for the selection of the starting dose:
Starting at the limit dose of 2000 mg/kg, in retrospect, proved to be appropriate, as no animals died at this dose.
Doses:
2000 mg/kg bw (3 males + 3 females)
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
Post-dosing observation period was 14 days during which mortality/survival and clinical signs were recorded at: 0, 2 and 4 hours after dosing on day 1 and twice daily (mortality/survival) or once daily (clinical signs) thereafter until day 15. Body weight of each animal was recorded on day 1 (prior to dosing) and on days 8 and 15. At the end of the 14-day post-dosing observation period (day 15), all animals were killed by asphyxiation with oxygen/carbon dioxide and necropsied. Macroscopic pathology findings were recorded.
Statistics:
Not applicable, as there were no deaths and only one dose group. In addion, the acute toxic class method is not intended for the calculation of a precise LD50 value.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: No deaths at the limit dose of 2000 mg/kg
Mortality:
Dose level Mortality Date of treatment
2000 mg/kg 0/3 (f) 09 January 2001
2000 mg/kg 0/3 (m) 11 January 2001
Clinical signs:
Clinical signs of systemic toxicity were not evident.
Body weight:
No adverse effects on body weight.
Gross pathology:
Necropsy of each animal at the end of the 14-day post treatment observation period did not reveal any macroscopic pathology findings.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information no mortality at the limit dose of 2000 mg/kg Criteria used for interpretation of results: EU