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Administrative data

Description of key information

The LD50 value was determined to be between 300 and 2000 mg/kg 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:
July 29, 2019 - September 2019
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:
December 2001
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no
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, Germany
- Age at study initiation: 9 weeks
- Fasting period before study: yes
- Housing: group-housed in type IV Makrolon cages; one day before treatment,rats were single-housed in type II Makrolon cages
- Diet: ad libitum, V1534, ssniff Spezialdiäten GmbH, Germany
- Water: ad libitum, tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 45-65
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
other: 0.25% aqueous hydroxypropylcellulose (Methocel)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD
- Rationale for the selection of the starting dose: Due to the fact, that no information concerning the toxic potential of the test item is available, the study started in 3 females with 300 mg/kg bw.
Doses:
300 mg/kg bw (starting dose)
2000 mg/kg bw
No. of animals per sex per dose:
3 (females)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: recorded directly before treatment (day 1) and on days 2, 4, 6, 8,11,13 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, histopathology
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was seen after treatment with 300 mg/kg during the course of this study. All three rats treated with 2000 mg/kg were killed in moribund condition 4 hours after treatment.
Clinical signs:
No clinical signs of toxicity were observed in all rats treated with 300 mg/kg. All rats treated with 2000 mg/kg showed locomotor disturbance, abdominal or lateral position and dyspnea.
Body weight:
The body weight development of the rats treated with 300 mg/kg was inconspicuous throughout the study.
Gross pathology:
The gross pathology examination revealed no findings in animals dosed with 300 mg/kg. The animals at 2000 mg/kg exhibited a dark red or dark grey discoloration of the lung.
Other findings:
The histopathology examination of the lungs of the animals dosed with 2000 mg/kg revealed in all animals blood congestion and in two animals mild acute alveolar hemorrhages and a perivascular edema.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The test item has acute toxic potential under the conditions of the present study, and the LD50 value was between 300 and 2000 mg/kg bw 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 study was started with 300 mg/kg in 3 female rats where no mortality was seen, and continued with further 3 females treated with 300 mg/kg. Due to the fact, that no mortality was seen in animal after treatment with 300 mg/kg, 3 further females were 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 was seen after treatment with 300 mg/kg during the course of this study. All three rats treated with 2000 mg/kg were killed in moribund condition 4 hours after treatment. No clinical signs of toxicity were observed in all rats treated with 300 mg/kg. All rats treated with 2000 mg/kg showed locomotor disturbance, abdominal or lateral position and dyspnea. In 2 out of 3 rats incomplete eyelid closure was seen. The body weight development of the rats treated with 300 mg/kg was inconspicuous throughout the study. The gross pathology examination revealed no findings in animals dosed with 300 mg/kg. The animals at 2000 mg/kg exhibited a dark red or dark grey discoloration of the lung. The histopathology examination of the lungs of the animals dosed with 2000 mg/kg revealed in all animals blood congestion and in two animals mild acute alveolar hemorrhages and a perivascular edema. Under the conditions of the present study, the LD50value is expected to be between 300 - 2000 mg/kg after single oral administration in rats.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
300 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

An acute oral toxicity study with the test item was performed according to the Acute-Toxic-Class Method and OECD Guideline 423.The study was started with 300 mg/kg in 3 female rats where no mortality was seen, and continued with further 3 females treated with 300 mg/kg. Due to the fact, that no mortality was seen in animal after treatment with 300 mg/kg, 3 further females were 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 was seen after treatment with 300 mg/kg during the course of this study. All three rats treated with 2000 mg/kg were killed in moribund condition 4 hours after treatment. No clinical signs of toxicity were observed in all rats treated with 300 mg/kg. All rats treated with 2000 mg/kg showed locomotor disturbance, abdominal or lateral position and dyspnea. In 2 out of 3 rats incomplete eyelid closure was seen. The body weight development of the rats treated with 300 mg/kg was inconspicuous throughout the study. The gross pathology examination revealed no findings in animals dosed with 300 mg/kg. The animals at 2000 mg/kg exhibited a dark red or dark grey discoloration of the lung. The histopathology examination of the lungs of the animals dosed with 2000 mg/kg revealed in all animals blood congestion and in two animals mild acute alveolar hemorrhages and a perivascular edema. Under the conditions of the present study, the LD50value is expected to be between 300 - 2000 mg/kg after single oral administration in rats.

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 oral toxicity, the test item is classified as acute toxic cat 4 H302 according to Regulation (EC) No 1272/2008 (CLP), as amended for the twelfth time in Regulation (EU) 2019/521.