Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 July 2017 to 15 August 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:
- Appearance: Fine, dark grey powder

Test animals

Species:
rat
Strain:
Wistar
Remarks:
RccHan™:WIST
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: 148 to 174 g
- Fasting period before study: animals were given an overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing
- Housing: animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes.
- 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: the 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:
arachis oil
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: Arachis oil BP was used because the test item did not dissolve/suspend in distilled water.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: The test material, prepared as a suspension in arachis oil BP, was formulated within 2 hours of being applied to the test system.


CLASS METHOD
- Rationale for the selection of the starting dose: In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose.
Doses:
300 mg/kg for a single animal, increased to 2000 mg/kg in the absence of toxicity.
No. of animals per sex per dose:
One female at 300 mg/kg.
Five females at 2000 mg/kg.
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 up to 14 days.
Morbidity and mortality checks were made twice daily, early and late during normal working days, and once daily at weekends and public holidays.
Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
At the end of the observation period the surviving 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.

Results and discussion

Preliminary study:
The following results were observed for the single female dosed at 300 mg/kg:
- There was no mortality.
- No signs of systemic toxicity were noted during the observation period.
- The animal showed expected gains in body weight over the observation period.
- No abnormalities were noted at necropsy.
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the observation period.
Body weight:
All 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 female Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

The acute oral toxicity of the test material was investigated in accordance with the standardised guidelines OECD 420 and EU Method B1 bis, under GLP conditions. The fixed dose procedure was performed in female Wistar strain rats.

Following a sighting test at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test material, as a suspension in arachis oil BP, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths or signs of systemic toxicity, all animals showed expected gains in body weight and no abnormalities were noted at necropsy.

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