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Description of key information

After treatment with the test item locomotor disturbance and dyspnea on day 1 of the experimental phase was seen and one rat treated with 2000 mg/kg died 4 hours after treatment. However, the LD50 value is higher than 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:
2017-12-12 to 2018-03-26
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:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: 9 weeks
- Weight at study initiation: 149 g - 172 g
- Fasting period before study: 17 to 20 hours before start of treatment until 4 hours after administration.
- Housing: during acclimation period: 3 animals/cage, type IV Makrolon cages with a shelter on softwood bedding material (ABEDD LTE E-001, ABEDD LAB&VET Service GmbH, Austria) and with play tunnels (Ref. 14153, Plexx BV, Netherlands); starting 1 day before treatment: single, type III Makrolon cages with shelter and play tunnel on softwood bedding material.
- Diet: ad libitum, maintenance diet (VI534, ssniff Spezialdiaten GmbH, Germany)
- Water: ad libitum, community water, changed at least three times per week.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.0 - 24.0
- Humidity (%): 40 - 70
Route of administration:
oral: gavage
Vehicle:
other: 0.25% aqueous hydroxypropylcellulose (Methocel® K.4M Premium solution, 2.5 g/L distilled water)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 g/L
- Amount of vehicle: 10 mL/kg bw
- Justification for choice of vehicle: well tolerated and established standard vehicle

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 bw. Therefore, the study was started with 2000 mg/kg bw in three female rats and continued with further three females at 2000 mg/kg bw.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
1st series 3 females, 2nd series 3 females
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. On the following days, the rats were examined once daily. All animals were weighed before treatment (day 1) and on day 2, 4, 6, 8, 11, 13 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathological investigation
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One out of six rats treated with 2000 mg/kg died 4 hours after treatment. All other rats survived the observation period. The median lethal oral dose (LD50) is higher than 2000 mg/kg.
Clinical signs:
All rats showed locomotor disturbance and dyspnea on day 1 of the experimental phase.
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 acute oral LD50 was determined to be > 2000 mg/kg bw in rats.
Executive summary:

A study was conducted to evaluate the acute oral toxicity of the test substance in rats according to OECD 423. The test substance was administered by gavage in a dose of 2000 mg/kg bw to a total of 6 female animals (2 sequential tests were performed with 3 rats each). During the observation period of 14 days one out of six animals died 4 hours after treatment. All other rats survived the observation period. All rats showed locomotor disturbance and dyspnea on day 1 of the experimental phase. The body weight development was inconspicuous throughout the study. Pathological examinations revealed no changes. The LD50 for acute oral toxicity was established to be > 2000 mg/kg bw in rats. The LD50 value is higher than 2000 mg/kg after single oral administration of the test item in female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study is considered suitable.

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

Acute oral toxicity study (reference 7.2.1-1)

A study was conducted to evaluate the acute oral toxicity of the test substance in rats according to OECD 423. The test substance was administered by gavage in a dose of 2000 mg/kg bw to a total of 6 female animals (2 sequential tests were performed with 3 rats each). During the observation period of 14 days one out of six animals died 4 hours after treatment. All other rats survived the observation period. All rats showed locomotor disturbance and dyspnea on day 1 of the experimental phase. The body weight development was inconspicuous throughout the study. Pathological examinations revealed no changes. The LD50 for acute oral toxicity was established to be > 2000 mg/kg bw in rats. The LD50 value is higher than 2000 mg/kg after single oral administration of the test item in female rats.

Justification for classification or non-classification

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

The available data are reliable and suitable for classification purposes under Regulation 1272/2008 (CLP). Based on this data, the substance is not considered to be classified for acute oral toxicity under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EC) No 2017/776.