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Description of key information

Key study: OECD Guideline 423 and EU Method B.1.tris. GLP study. The acute oral LD50 value of the test item was found to be above 2000 mg/kg bw in female Crl:WI Wistar rats.

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:
12 September 2017 - 27 September 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Remarks:
Crl:WI Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 11 weeks old
- Weight at study initiation: 211 - 260 g
- Fasting period before study: On the night before treatment, the animals were fasted. The food was returned 3 hours after the treatment.
- Housing: 3 animals/cage (Type II. polypropylene/polycarbonate cages).
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least 26 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.2 – 25.0 °C
- Humidity (%): 34 – 80 %
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m..
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle: The selection of the vehicle was made during trial formulation with the test item. In order of preference, recommended vehicles were: distilled water, 0.5 or 1% methyl cellulose or carboxymethylcellulose, PEG 400, oil (corn or sunflower) and DMSO. The formulations prepared with distilled water or with 1% methyl cellulose (with continuous magnetic stirring) resulted inhomogeneous formats. Using PEG 400, a homogeneous format was available, which was suitable for oral gavage of the rats.

MAXIMUM DOSE VOLUME APPLIED:

DOSAGE PREPARATION (if unusual): The test item was freshly formulated at a concentration of 200 mg/mL in the vehicle on the day of administration. The formulation container was magnetic stirred continuously up to the end of dose administration procedures.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Individual observations were performed on the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0), weekly thereafter (Day 7) and at necropsy (Day 14).
- Necropsy of survivors performed: yes
Macroscopic examination was performed on all animals. After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Test item did not cause mortality at a dose level of 2000 mg/kg bw in any animal.
Clinical signs:
other: At the dose level of 2000 mg/kg bw, the following symptoms were observed up to Day 1: slightly or/to moderately or/to markedly decreased activity (6 out of 6 animals), hunched back (6 out of 6 animals), slight and/or moderate incoordination (6 out of 6 an
Gross pathology:
There was no evidence of the macroscopic changes at necropsy at a dose level of 2000 mg/kg bw in any animal.
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The acute oral LD50 value of the test item was found to be above 2000 mg/kg bw in female Crl:WI Wistar rats.
Executive summary:

An acute oral toxicity test was performed according to OECD Guideline 423 and EU Method B.1.tris (GLP study). Two groups of three female Crl:WI rats were treated with the test itemat a dose level of 2000 mg/kg body weight (bw) (Group 1 and Group 2). The test item was administered by gavage at the dose level of 2000 mg/kg bw. Initially, three females (Group 1) were treated at a dose level of 2000 mg/kg bw. As no mortality was observed, a confirmatory group (Group 2) was treated at the same dose level. No mortality was observed in the confirmatory group. The following symptoms were observed up to Day 1: slightly or/to moderately or/to markedly decreased activity (6 out of 6 animals), hunched back (6 out of 6 animals), slight and/or moderate incoordination (6 out of 6 animals), piloerection (4 out of 6 animals) and prone position (2 out of 6 animals). From Day 2, all animals were symptom-free until the end of the observation period. There were no treatment related body weight changes. Body weights were within the range commonly recorded for this strain and age. There was no evidence of the macroscopic changes at necropsy at a dose level of 2000 mg/kg bw. Under the conditions of this study, the acute oral LD50 value of the test item was found to be above 2000 mg/kg bw in female Crl:WI Wistar rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Only one study available of Klimish score 1.

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

Justification for classification or non-classification

Based on available data (oral LD50 > 2000 mg/kg bw), the substance is not classified for acute toxicity according to CLP Regulation (EC) no. 1272/2008.

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