Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2019-03-12 to 2019-04-09
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
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 material form:
solid

Test animals

Species:
rat
Strain:
other: Crl:WI (Han)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River GmbH, Sulzfeld, Germany
- Age at study initiation: 9 weeks
- Weight at study initiation: The mean initial body weight at the start of study was 166 g (range from 158 to 171 g).
- Fasting period before study: Diet was withheld from about 17 to 20 hours before start of treatment until 4 hours after administration.
- Housing: During the acclimation phase, the three rats per treatment group were group-housed in type IV Makrolon® cages with a shelter on softwood bedding material (ABEDD LTE E-001, ABEDD LAB&VET Service GmbH, Austria). Play tunnels (Ref. 14153, Plexx BV, Netherlands) were placed in the cages as additional enrichment. One day before treatment, the rats were single-housed in type III Makrolon" cages with a shelter and a play tunnel on softwood bedding material. Wire grids were placed above the softwood granules. They were removed 4 hours after administration. The rats were kept individually until the end of the observation period. The bedding was changed once a week.
- Diet: ad libitum (VI534, ssniff Spezialdiaten GmbH, Germany)
- Water: ad libitum (drinking water from community water supply)
- Acclimation period: Before start of treatment, the animals were acclimated for at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.7 - 23.6
- Humidity (%): 41.6 - 47.7

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.25% aqueous hydroxypropylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 g/L

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: The test item preparation was made directly before administration. Appropriate amounts of the test item were suspended in the vehicle using a spatula, a mini shaker (Vortex Genie 2®, Scientific Industries Inc, New York, USA), Ultra-Turrax device (Ultra-Turrax T25, IKA®-Werke GmbH & Co. KG, Staufen, Germany) and a magnetic stirrer. The test item preparation was administered within less than 1 hour after preparation. The stability of the test item in the vehicle was not investigated.

CLASS METHOD
- Rationale for the selection of the starting dose: Due to the chemical properties of the test item, mortality was not expected at the highest starting dose of 2000 mg/kg. Therefore, the treatment was started with 2000 mg/kg in three female rats and continued with further three females at 2000 mg/kg.
Doses:
2000 mg/kg bw/day
No. of animals per sex per dose:
6 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: All animals were weighed before treatment (day 1) and on day 2, 4, 6, 8, 11, 13 and 15.
- Mortality and Clinical Signs: On the day of treatment, each animal was observed for mortality and for symptoms of intoxication at scheduled intervals according to the record sheets. On the following days, the rats were examined once daily. Symptoms were recorded individually for each animal.
- Necropsy of survivors performed: yes

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 was seen.
Clinical signs:
No clinical signs of toxicity were observed.
Body weight:
There were no effects on the body weight development throughout the study.
Gross pathology:
No organ alterations were identified during the gross pathological examination.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test item has no acute toxic potential under the conditions of the present study, and the LD50 value is higher than 2000 mg/kg after single oral administration in female rats.
Executive summary:

An acute oral toxicity study with the test item was performed according to the Acute-Toxic-Class Method and OECD Guideline 423. The treatment was started with 2000 mg/kg body weight in 3 female rats and continued with further 3 females treated with 2000 mg/kg. Mortality and clinical signs were monitored for at least 6 hours after administration and then daily. All animals were weighed before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15. At the end of the observation period, all surviving rats were sacrificed and subjected to a detailed necropsy. No mortality occurred during the course of this study. No clinical signs of toxicity were observed. The body weight development was inconspicuous throughout the study. The gross pathological examination revealed no organ alterations. In conclusion, the test item has no acute toxic potential under the conditions of the present study, and the LD50 value is higher than 2000 mg/kg after single oral administration in female rats.