Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2014-11-25 to 2014-12-23
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
December 17, 2001
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Bioassay GmbH, Im Neuenheimer Feld 515-519, 69120 Heidelberg, Germany
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Lot 003
- Expiration date of the lot/batch: January 2020

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature; no direct sunlight; protect against humidity
- Stability under test conditions: stable

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks old
- Weight at study initiation: 183 - 192 g
- Fasting period before study: at least 16 hours
- Housing: single
- Diet: ad libitum, VRF1(P) (SDS Special Diets Services, 67122 Altrip, Germany)
- Water: ad libitum, tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5 % solution (Dow Wolff Cellulosics GmbH) in deionized water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 g/100 mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: A good homogeneity in water could not be guaranteed, because the test item preparation was a suspension. Therefore a 0.5% solution of CMC in deionized water was applicable.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
300, 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: observations daily; weighing weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

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 mortality occurred in both 2000 mg/kg bw test groups and in the single 300 mg/kg bw test group.
Clinical signs:
In the first 2000 mg/kg bw test group impaired general state and piloerection was noted from hour 1 or 2 until hour 5 after administration. One of these animals additionally showed cowering position from hour 2 until hour 3.
In the second 2000 mg/kg bw test group impaired general state and piloerection was observed in all animals from hour 1 or 2 until hour 3 or 5 after administration.
In the single 300 mg/kg bw test group impaired general state and piloerection was noticed in one animal from hour 0 until hour 3, while the other two animals were free of any symptoms.
Body weight:
The mean body weight of all animals increased within the normal range throughout the study period.
Gross pathology:
There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period (9 females).

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met