Registration Dossier

Administrative data

Description of key information

The test item has no acute toxic potential and the LD50 value is higher than 2000 mg/kg bw after single oral administration in female rats (reference 7.2.1 -1).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
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
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
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
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).
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
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
OECD TG 423

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a study according OECD TG 423 the acute toxic potential of the test item after single oral administration to rats was determined 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 bw. 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 and the LD50 value is higher than 2000 mg/kg bw after single oral administration in female rats (reference 7.2.1 -1).

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available data for acute oral toxicity are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on this data, the substance is not considered to be classified for acute toxicity under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) No 2019/521.