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:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2019

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
Adopted: 17th December 2001
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Storage conditions: Room Temperature (20 ± 5 °C)
- Expiry date: 16. Dec. 2019

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Slovak Academy of Sciences Dobrá Voda, Slovak Republic
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: 187 - 207 g
- Fasting period before study: Animals were fasted 10-12 h prior to dosing (food but not water was withheld over-night)
- Housing: The animals were housed in plastic cages suspended on stainless steel racks, 3 animals per cage in a room equipped with central air-conditioning. Bedding was Lignocel S3/4, Lufa - ITL GmbH, Germany
- Diet (e.g. ad libitum): The laboratory food ssniff (ssniff Spezialdiäten GmbH, Germany) was available at libitum.
- Water (e.g. ad libitum): The animals received tap water for human consumption. Supply of drinking was unlimited. The quality of drinking water is periodically analysed and recorded.
- Acclimation period: The animals were acclimated under the conditions identical to the conditions during the experiment 5 days prior to the start of treatment. The acclimation was according to the standard operation procedure.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.23 ± 0.17° C
- Humidity (%): 53.61 ± 4.95 %
- Photoperiod (hrs dark / hrs light): 12-hour light /12-hour dark cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: Olive oil is a common vehicle in toxicity studies like OECD TG 423
- Lot/batch no. (if required): L71143

DOSAGE PREPARATION (if unusual):
The required amount of the test item (according to the body weight and dose) was mixed with vehicle (Olive oil) shortly before administration.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 females in total
Control animals:
no
Remarks:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed individually immediately after administration of the test item and 0.5, 1, 2, and 4 hours later. Each animal was inspected daily for the next 14 days.
Individual weights of animals were measured immediately prior to administration of the test item and weekly thereafter. Weight differences after first and second weeks after administration were calculated and recorded.
- Necropsy of survivors performed: Yes. All test animals were subjected to gross necropsy and the results were recorded for each animal.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All (6/6 females) animals survived the limit dose of 2000 mg/kg body weight.
Clinical signs:
No mortality was observed during the study. During the follow up period, no animals displayed signs of intoxication, change of health, nor any other adverse reaction.
Body weight:
The body weights of all animals increased during the study. No body weight losses were observed between the first and second week after administration.
Gross pathology:
All animals were necropsied. During necropsy, no macroscopic findings were observed.

Applicant's summary and conclusion

Interpretation of results:
other: EU GHS criteria not met
Conclusions:
The study was conducted under GLP according to OECD guideline 423 on the registered substance itself. The method is to be considered scientifically reasonable with no deficiencies in documentation or any deviations. Hence, the results can be considered as reliable to assess the acute toxicity of the test item in rats.
The test item administered to 6 females at a limit dose of 2000 mg/kg body weight did not cause death. No signs of toxicity were observed during the first 4 hours in females or the 14-day observation period thereafter. The body weights of all animals increased during the study. No body weight losses were observed between the first and second week after administration. During necropsy, no macroscopic findings were observed.
The LD50 of the test item is greater than 2000 mg/kg body weight after single oral administration to Wistar rats.
Executive summary:

The purpose of the study was to evaluate the potential toxic effect of the test item when administered as a single oral dose to Wistar rats. The procedure according to OECD Guideline 423 Acute Toxic Class (ATC) method was used (GLP).

A limit dose of 2000 mg/kg body weight was used as a starting dose. The test item administered to 6 females at a limit dose did not cause death. The body weights of all animals increased during the study. No body weight losses were observed between the first and second week after administration. During necropsy, no macroscopic findings were observed.

The LD50of the test item is greater than 2000 mg/kg body weight after single oral administration to Wistar rats.

Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg body weight of OECD Guideline 423 it can be concluded that the test item is according to GHS criteria classified in Category 5 (CLP: unclassified) with a LD50 cut-off value equal to or greater than 2000 mg/kg body weight, after single oral administration to Wistar rats.