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Description of key information

The acute median lethal oral dose (LD50) to rats of the test item was demonstrated to be greater than 2000 mg/kg body weight.

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:
25 November 2019 to 11 December 2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
2008
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Janvier Labs SAS, CS 4105 LE Genest St Isle, 53941 Saint Berthevin Cedex / France
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9 weeks
- Fasting period before study: over night
- Housing: groups of one to five rats (of the same sex and dose group)
- Diet: 2018C Teklad Global 18% protein rodent diet (certified), ad libitum
- Water: ad libitum tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + 2°C
- Humidity (%): approx. 45-65
- Photoperiod: artificial light 6.00 a.m. - 6.00 p.m.
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
1 %
Details on oral exposure:
The test item was formulated at a concentration of 30 and 200 mg/mL in the vehicle and administered at a constant dose volume of 10 mL/kg body weight. Ultraturrax treatment and constant stirring was used to formulate the test item.
Test substance formulations were freshly prepared on the day of dosing, issued at room temperature and administered as soon as possible (within 4 hours of preparation).
Samples of test substance formulations were not taken for analysis and consequently the homogeneity, concentration and stability of the test item were not determined.
Doses:
In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the initial starting dose, since a severe toxicity which may necessitate humane euthanasia was not expected at this dose level. Two single animals were treated as follows: 100 and 2000 mg/kg bw. In the absence of mortality or toxicity at a dose level of 2000 mg/kg, an additional group of 4 animals was treated with 2000 mg/kg bw.
No. of animals per sex per dose:
1 or 5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Clinical observations and inspections for morbidity / mortality were performed at least three times within the first six hours after application (i.e., 30 minutes and 1 hour, 2 hours and 4 hours after dosing), thereafter at least once daily for 14 days.
- Necropsy of survivors performed: yes
- Clinical signs including body weight: The nature and severity, where appropriate, of the clinical signs and the time were recorded at each observation for all individual animals. If applicable, the time of death/humane kill was recorded as precisely as possible. Observations included changes in the skin and fur, eyes and mucous membranes, and respiratory, circulatory, autonomic and central nervous system, and somatomotor activity and behavior pattern. Particular attention was directed to the observation of tremors, convulsions, salivation, diarrhea, lethargy, sleep and coma. Body weights were recorded on Day 0 (prior to dosing), Day 7, and 14, or (if applicable) at death (unscheduled).
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
Hunched posture was noted 4 h after application in the animal treated with 300 mg/kg b.w.. Piloerection was noted on day 1 in one animal treated at a dose level of 2000 mg/kg b.w.. There were no signs of systemic toxicity noted in the remaining animals.
Body weight:
All animals showed expected gains in body weight.
Gross pathology:
Clear liquid in the uterus, focal white nodules in the capsule of the kidney (indicative of fat tissue), and pale tissue and minor focal, slightly sunken areas in the heart tissue were observed in one animal each at a dose level of 2000 mg/kg..
Interpretation of results:
GHS criteria not met
Conclusions:
The acute median lethal oral dose (LD50) to rats of the test item was demonstrated to be greater than 2000 mg/kg body weight.
Executive summary:

The study was performed according to OECD guideline 420 to assess the acute oral toxicity of the test substance to the rat. Following a sighting test at dose levels of 300 mg/kg b.w. and 2000 mg/kg b.w. in one female rat per dose group, a further group of four fasted females was given a single oral dose of the test item as a formulation in 1% CMC (Carboxymethylcellulose), at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored in all animals during the study. All animals were subjected to gross necropsy. As a result, mortality did not occur. Hunched posture was noted 4 h after application in the animal treated with 300 mg/kg b.w.. Piloerection was noted on day 1 in one animal treated at a dose level of 2000 mg/kg b.w.. There were no signs of systemic toxicity noted in the remaining animals. The acute median lethal oral dose (LD50) to rats was demonstrated to be greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 2 000 mg/kg bw
Quality of whole database:
GLP and OECD Guideline conform study

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

The study was performed according to OECD guideline 420 to assess the acute oral toxicity of the test substance to the rat. Following a sighting test at dose levels of 300 mg/kg b.w. and 2000 mg/kg b.w. in one female rat per dose group, a further group of four fasted females was given a single oral dose of the test item as a formulation in 1% CMC (Carboxymethylcellulose), at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored in all animals during the study. All animals were subjected to gross necropsy. As a result, mortality did not occur. Hunched posture was noted 4 h after application in the animal treated with 300 mg/kg b.w.. Piloerection was noted on day 1 in one animal treated at a dose level of 2000 mg/kg b.w.. There were no signs of systemic toxicity noted in the remaining animals. The acute median lethal oral dose (LD50) to rats was demonstrated to be greater than 2000 mg/kg body weight.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute toxicity, the test item is not considered to be classified according to Regulation (EC) No 1272/2008 (CLP), as amended for the seventeenth time in Regulation (EU) 2021/849.

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