Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04.03.2002 to 10.06.2002
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
There were minor deviations from the guideline with respect to selection of dose levels.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
Doses of 2000 and 200 mg/kg bw were used, the guideline recommends 2000 followed by 300 mg/ kg bw.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

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, in dark, tightly closed, dry
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: soluble and stable for 1 day in corn oil

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test substance was used as supplied at the highest dose tested (2000 mg/kg bw) and corn oil was used as vehicle at 200 mg/kg bw.
- Preliminary purification step (if any): not specified

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH
- Age at study initiation: male: 41 days, female: 48 days
- Weight at study initiation: male: 173-213 g; female: 163-173 g
- Fasting period before study: 16 hours before administration of test substance, only tap water ad libitum was available
- Housing: during 14 day observation period groups of 2 -3 animals in MAKROLON cages (type III).
- Diet (e.g. ad libitum): ssniff R/M-H V 1530 (ssniff Spezialiäten GmbH)
- Water: drinking water ad libitum
- Acclimation period: at least 5 adaption days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C+-3°C
- Humidity (%): 55% +-15%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/l
- Administration volume: 1.69 ml/kg bw
- Lot/batch no. (if required):81K2204, SIGMA ALDRICH Chemie GmbH

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg b.w. without vehicle
Administration volume: 1.69 ml/kg b.w.
Doses:
2000 mg/kg bw without vehicle
200 mg/kg bw in vehicle (corn oil)
Administration volume: 1.69 ml/kg bw
No. of animals per sex per dose:
2000 mg/kg bw: 3 (male) animals
200 mg/kg bw: 3 male, 3 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: before and immediately at 5, 15, 30 and 60 minutes, as well as 3, 6, and 24h after administration, all surviving animals once a day until all symptoms subsided, thereafter each working day. Observations on mortality once daily, individual body weights were recorded before administration and thereafter in weekly intervals up to the end of the study
- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was performed, the method used was not intended to allow the calculation of a precise LD50 value.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 200 - < 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable
Mortality:
2000 mg/kg bw resulted in the death within 30 min of all (male) animals
200 mg/kg bw: one of 3 male and none of 3 female animals died prematurely (within 7 days)
Clinical signs:
2000 mg/kg bw: reduced motility, ataxia, reduced muscle tone, dyspnoea, lateral position, ptosis
200 mg/kg bw: no animals showed any signs of systemic toxicity.
Body weight:
All surviving animals gained the expected body weight within the study period.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
A reliable study conducted according to OECD 423 and in accordance with GLP, identified an acute oral LD50 value of 200 - 2000 mg/kg bw in male and female rats.
6