Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 January 2017 to 01 February 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
2008
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
-White powder
Specific details on test material used for the study:
TEST MATERIAL
- Batch No.of test material: YBF1002/16
- Expiration date of the lot/batch: 17 October 2018

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark over silica gel

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 149 to 176 g
- Fasting period before study: overnight fast before dosing
- Housing: in groups of up to four in suspended solid-floor polypropylene cages furnished with wood flakes
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 25°C
- Humidity: 30 to 70 %
- Air changes: at least fifteen changes per hour
- Photoperiod: lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 300 and 2000 mg/kg
- Amount of vehicle: 10 mL/kg
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
1 animal was dosed at 300 mg/kg bw
5 animals were dosed at 2000 mg/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for 14 days. Morbidity and mortality checks were made twice daily. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes: At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
No statistical analysis was performed (the method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Preliminary study:
No effects were observed after the 300 mg/kg bw dose; there was no mortality, no signs of systemic toxicity, normal body weight gains and no abnormalities at necropsy. Based on the results at 300 mg/kg, a dose level of 2000 mg/kg body weight was investigated.
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality.
Clinical signs:
No signs of systemic toxicity were noted during the observation period.
Body weight:
The animals showed expected gains in body weight over the observation period.
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified in accordance with EU criteria
Conclusions:
Under the conditions of this study, the oral LD50 value in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

The acute oral toxicity potential of the test material to the rat was investigated in accordance with the standardised guidelines OECD 420 and EU Method B1 bis under GLP conditions using the Fixed Dose Method.

Following a sighting test during which two animals received test material at dose levels of 300 mg/kg and 2000 mg/kg respectively, a further group of four fasted females was given a single oral dose of test material, as a solution in distilled water, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the 14 day observation period of the study. All animals were subjected to gross necropsy.

No mortality occurred and there were no signs of systemic toxicity. The animals showed expected gains in body weight during the study and there were no abnormalities noted at necropsy.

Under the conditions of this study, the oral LD50 value in Wistar rats was established to exceed 2000 mg/kg body weight.