Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 June 2004 to 02 July 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

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:
1996
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature, light protected
- Stability under test conditions: stable under storage conditions
- Solubility and stability of the test substance in the solvent/vehicle: stable in corn oil
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not applicable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test material was diluted in corn oil. The dose formulations were made shortly before each dosing occasion using a magnetic stirrer. Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.
- Preliminary purification step (if any): none
- Final dilution of a dissolved solid, stock liquid or gel: not applicable
- Final preparation of a solid: not applicable



Test animals

Species:
rat
Strain:
Wistar
Remarks:
HanBrl: Wist (SPF)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd., Laboratory Animal Services, Switzerland
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 12 weeks
- Weight at study initiation: not specified
- Fasting period before study: 18 hours
- Housing: In group of three in Makrolon type-4 cages with wire mesh and tops and standard softwood bedding.
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, ad libitum
- Water: Community tap water, ad libitum
- Acclimation period: Yes. Under laboratory conditions, after health examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3°C
- Humidity (%): 30-70 %
- Air changes (per hour): 10-15 air changes per hour
- Photoperiod (hours dark / hours light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.02 g/mL
- Amount of vehicle (if gavage): not specified
- Justification for choice of vehicle: Corn oil was found to be a suitable vehicle. The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date.
- Lot/batch no. (if required): 45256503
- Purity: not specified

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual): The test material was diluted in corn oil. The dose formulations were made shortly before each dosing occasion using a magnetic stirrer. Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: starting dose was 2000 mg/kg bw in accordance with the test method.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for clinical signs of toxicity at approximately 1, 2, 3 and 5 hours after administration on test day 1 and twice daily during days 2-15. Animals were weighed on test days1, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Not used

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
Slightly ruffled fur was noted in two animals at the 1-hour reading and persisted up to the 3-hour reading in one animal.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were recorded at necropsy.
Other findings:
- Organ weights: not examined
- Histopathology: not examined
- Potential target organs: not examined

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral toxicity study for the submission substance, conducted according to an appropriate OECD test guideline and in compliance with GLP, reported an LD50 value of greater than 2000 mg/kg bw.