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: Study conducted to GLP and OECD/EC guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: 8-11 Weeks
- Weight at study initiation: 155-187g
- Fasting period before study: 16-19 hours
- Housing: IVC cages, type III H, polysulphone; Altromin saw fibre bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 degrees C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): 10x /hr
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- water
- Amount of vehicle (if gavage): 10mL/kg bodyweight

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg
Doses:
2000, 300, 50 mg/kg
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 weighing: day 1 (prior to dosing) and days 8 & 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
200 mg/kg bw
Mortality:
100% mortality was observed at 2000 and 300 mg/kg 1-2 minutes post dosing, 0% mortality at 50 mg/kg
Clinical signs:
clonic convulsions and opisthotonos were associated with all mortalities along with lateral recumbency, kyphosis and half eyelid closure in the high dose group.

Clonic convulsions, opisthotonos, prone position, piloerection were seen at up to 30 minutes post-dose in 2 of the 6 animals treated at 50 mg/kg, with much reduced clinical signs (such as slight piloerection, prone position) seen in the other 4 animals. nosigns of toxicity were seen from 1d until the end of the observation period in any of the animals.
Body weight:
Body weight gain was normal for the surviving animals in this study.
Gross pathology:
No significant findings for animals dosed at 50 mg/kg.
Animals dosed at 2000 mg/kg had residual test item in the stomach.
Animals dosed at 300 mg/kg had stomachs filled with liquid and bloody spots in the brain.

Applicant's summary and conclusion

Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose after single oral administration to female rats observed over 14 days was:
LD50 cut off (rat) = 200 mg/kg body weight.