Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 01 to 21 May 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study run to a method comparable with current guidelines and to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Analytical purity: 98%
- Lot/batch No.: CPo84700201-022901

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Approx. 10 or 11 weeks old
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean
- Fasting period before study: Overnight prior to dosing
- Housing: Labeled Makrolon cages containing sterilized sawdust as bedding material and paper as cage-enrichment
- Diet (e.g. ad libitum): Pelleted rodent diet
- Water (e.g. ad libitum): Tap water
- Acclimation period: At least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24
- Humidity (%): 40 to 70
- Air changes (per hr): at least 10 air changes/hour
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle

IN-LIFE DATES: From 01 to 21 May 2014

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle: The vehicle was selected based on trial formulations formed at WIL Research Europe and on test substance data supplied by the sponsor

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg (10 mL/kg) body weight

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females.
The first group was treated at a dose level of 2000 mg/kg. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines.
Doses:
2000 mg/kg
No. of animals per sex per dose:
3 females at a dose level of 2000 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes, at the end of observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy.
- Other examinations performed: no.
Statistics:
No statistical analysis was performed.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture and pioerection were noted for all animals between Day 1 and 12.
Lean appearance was noted for one animal between Days 7 and 9.
Body weight:
Most animals showed bodyweight loss between Days 1 and 8. All animals gained bodyweight between Days 8 and 15.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
No information provided.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value of the test substance in Wistar rats was established to exceed 2000 mg/kg bodyweight.