Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2018-10-03 to 2018-10-19
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:
2018

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: sunflower oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION
Formulations were prepared just before the administration and stirred continuously during the treatment.

CLASS METHOD
- Rationale for the selection of the starting dose: The starting dose was selected on the basis of the available information about the test item.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 in the first step, further 3 in the second step
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weights were recorded on days 0, 7, 15, clinical observations were performed at least once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h after the treatment, and once a day for 14 days thereafter
- Necropsy of survivors performed: yes
Statistics:
not applicable as no deaths occured

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 5 000 mg/kg bw
Based on:
test mat.
Mortality:
All rats in step 1 and step 2 survived until the end of the 14-day observation period.
Clinical signs:
No treatment related symptoms were observed in the 2000 mg/kg bw test item dose groups (step 1 and 2) throughout the 14-day post-treatment period.
Body weight:
The mean body weight of both groups corresponded to their species and age throughout the study.
Gross pathology:
All animals treated with 2000 mg/kg bw of the test item survived until the scheduled necropsy on Day 15.
Pyelectasis was observed on the right side in animal No.: 2691 of group 2. This macroscopic finding can be assessed as an individual variation without toxicological relevance. Slight hydrometra was found in animal No.: 2689 of the group 2. Moderate hydrometra was detected in animal No.: 2688 of group 1 and severe hydrometra was recorded in animal No.: 2686 in group 1. Hydrometra is a physiological finding and connected to the oestrus cycle of the animal.
No pathological changes were found related to the test item during the macroscopic examination of animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 value was found to be ≥5000 mg/kg bw.
Executive summary:

An acute oral toxicity study was carried out using the class method according to OECD guideline 423. The method was conducted using a stepwise procedure with 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level, so further three female rats were treated with the same (2000 mg/kg bw) dose. No animal died in the second step, so the test was finished, as a stopping criterion of Annex 2d of OECD Guideline No. 423 (presented in Appendix 7) was met. All animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out on the 15th day after the treatment. No mortality and no test item related adverse effects regarding body weight development or clinical observations were revealed. Therefore test item is not to be classified according to the GHS classification and the median lethal dose derived was: LD50 cut off ≥ 5000 mg/kg bw.