Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 18, 2018 - November 6, 2018
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 guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2008
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (Han)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, German
- Age at study initiation: 9 weeks
- Weight at study initiation: The mean initial body weight at the start of study was 162 g (range from 150 to 174 g).
- Fasting period before study: Diet was withheld from about 17 to 20 hours before start of treatment until 4 hours after administration.
- Housing: group-housed in type IV Makrolon® cages with a shelter on softwood bedding material
- Diet: maintenance diet (VI534, ssniff Spezialdiaten GmbH, Germany) ad libitum
- Water: community water supply was offered ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.9 - 23.2
- Humidity (%): 42.6 -58.5
- Air changes (per hr): fully air-conditioned room
- Photoperiod (hrs dark / hrs light): no information

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.25% aqueous hydroxypropylcellulose
Details on oral exposure:
VEHICLE
- Amount of vehicle: 0.25% aqueous hydroxypropylcellulose (Methocel® K4M Premium solution, 2.5 g/L distilled water)
- Justification for choice of vehicle: This vehicle was well tolerated and established as standard vehicle.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: Appropriate amounts of the test item were suspended in the vehicle using a spatula, a mini shaker, Ultra-Turrax device and a magnetic stirrer. The test item preparation was administered within less than 1 hour after preparation.

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
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 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. All animals were weighed before treatment (day 1) and on day 2, 4, 6, 8, 11, 13 and 15.
- Necropsy of survivors performed: yes
Statistics:
None

Results and discussion

Preliminary study:
Prior to this study, an in vitro skin irritation test was performed with the test item in which no irritating potential was detected (Gado, 2018).
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 median lethal oral dose (LD50) is higher than 2000 mg/kg bw.
Executive summary:

The objective of the present study was to identify potential toxic effects of the test item after single oral administration to rats in a stepwise procedure according to OECD TG 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.

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 bw after single oral administration in female rats.