Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2005-06-28 to 2005-11-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2004
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: V3186/1 1

Letter of Confirmation: CAS No 90530-15-7 and 93940-97-7 refer to the same substance and substance composition.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Laboratory Animal Services, Wölferstrasse 4, CH-4414 Füllinsdorf, Switzerland
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Young adult animals (female animals approx. 8 - 12 weeks)
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight)
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: single housing in stainless steel wire mesh cages, type DK-111 (Becker & Co., Castrop-Rauxel, IFIRG )
- Diet: Kliba Labordiät (Maus / Ratte Haltung "GLP"), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland, ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): fully air conditioned rooms
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a. m. - 6.00 p. m. / 6.00 p. m. - 6.00 a. m.)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10; 40 g/100 mL
- Amount of vehicle: 5 mL/kg
- Justification for choice of vehicle: Olive oil Ph. Eur./DAB had to be used to ensure homogeneity/stability of the preparation.

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg

CLASS METHOD
- Rationale for the selection of the starting dose: Based on the physical and chemical characteristics of the test substance and its composition, no pronounced acute oral toxicity was expected. Therefore, a starting dose of 2000 mg/kg body weight has been chosen in the first step with 3 female animals. As 2 of those animals died, 500 mg/kg body weight were administered to 3 female animals in a second step. Because no animal died at the second step, 500 mg/kg body weight have been tested in a third step with another group of 3 female animals. Because all animals survived the third step the study was terminated.
Doses:
2000; 500 mg/kg bw
No. of animals per sex per dose:
3 and 6 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and at the end of the study. Additionally, at day of death in animals that died or were sacrificed moribund starting with study day 1.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, pathology

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 500 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Two animals of the 2000 mg/kg bw administration group were found dead on study days 1 and 8, respectively. No mortality occurred in the 500 mg/kg bw administration groups.
Clinical signs:
Clinical observation in the 2000 mg/kg bw administration group revealed impaired general state, dyspnoea, staggering, tremor, piloerection, smeared fur, salivation and red clammy snout and were observed from hour 0 until including study day 9 after administration. No clinical observations were observed in the 500 mg/kg bw administration groups during clinical examination.
Body weight:
The body weight of the surviving animal of the 2000 mg/kg bw administration group and the mean body weights of the animals of the 500 mg/kg bw administration groups increased throughout the study period.
Gross pathology:
No macroscopic pathologic findings were observed in the animals that died (2000 mg/kg bw: 2 females) and in the animals examined at termination of the study (2000 mg/kg bw: 1 female; 500 mg/kg bw: 6 females).

Applicant's summary and conclusion