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Description of key information

Under the conditions of the study, the acute oral LD50 value of the test item was found to be above 2000 mg/kg bw in female CRL: (WI) 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:
31 August 2016 to 15 September 2016
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
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: Young healthy adult rats, 9 weeks old.
- Weight at study initiation: 205 – 217 g. Body weight variation did not exceed +/-20 % of the sex mean.
- Fasting period before study: On the night before treatment, the animals were fasted. The food but not water was withheld during an overnight period. The food was returned 3 hours after the treatment.
- Housing: The animals were housed in Type II polypropylene/polycarbonate cages with 3 animals/cage.
- Diet: Ad libium
- Water: Ad libitum
- Acclimation period: 13-14 days before start of treatment under laboratory conditions

FOOD AND WATER QUALITY
The food was considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study. Water quality control analysis is performed once every three months and microbiological assessment is performed monthly.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.8 - 25.1 ºC
- Humidity (%): 34 - 75 %
- 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:
water
Remarks:
Distilled water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: The test item was freshly formulated at a concentration of 200 mg/mL in the vehicle.
- Amount of vehicle: 10 mL/kg bw

DOSAGE PREPARATION: 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 stirred continuously up to finishing the treatment.

CLASS METHOD
- Rationale for the selection of the starting dose: The initial dose level was selected by the study director to be that which is most likely to produce mortality in some of the dosed animals. In the lack of any preliminary toxicological information, 2 000 mg/kg bw was selected to be the starting dose.
Initially, three females (Group 1) were treated at a dose level of 2 000 mg/kg bw of the tst material. The test item did not cause mortality in this group; therefore a confirmatory group (Group 2) was treated at the same dose level. The test item did not cause mortality in the confirmatory group, so no further testing was required.
Doses:
A single oral gavage administration of 2 000 mg/kg bw.
No. of animals per sex per dose:
Six females per dose.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were performed at the surviving animals 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) and weekly thereafter.
- Necropsy of survivors performed: Yes. Macroscopic examination was performed on all animals. The animals were sacrificed by exsanguination under pentobarbital anaesthesia. After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.
Statistics:
The method was not intended to allow the calculation of a precise LD50 value.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The test material did not cause mortality at a dose level of 2 000 mg/kg bw.
Clinical signs:
All animals were symptom free during the study.
Body weight:
Body weight gains of test item treated animals during the study showed no indication of a test item-related effect.
Gross pathology:
There was no evidence of the macroscopic observations at a dose level of 2 000 mg/kg bw.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the study, the acute oral LD50 value of the test item was found to be above 2 000 mg/kg bw in female CRL:(WI) rats.
Executive summary:

The acute oral toxicity of the test material was assessed in the female CRL:(WI) rat in accordance with the standardised guidelines OECD 423 and EU Method B.1 tris under GLP conditions.

Two groups of three female Crl: (WI) rats were treated with the test item at a dose level of 2 000 mg/kg bw via oral gavage (Group 1 and Group 2).

A single oral treatment was carried out by gavage for each animal after an overnight food withdrawal. Food was made available again 3 hours after the treatment. The test item was administered formulated in Distilled water at a concentration of 200 mg/mL at a dose volume of 10 mL/kg bw.

Initially, three females (Group 1) were treated at a dose level of 2 000 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; therefore no further testing was required.

Clinical observations were performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on Days 1, 0 and 7 and before necropsy. All animals were subjected to a necropsy and a macroscopic examination.

The test material did not cause mortality at a dose level of 2 000 mg/kg bw. All animals were symptom free during the study. Body weight gains of test item-treated animals during the study showed no indication of a test item-related effect. There was no evidence of the macroscopic observations at a dose level of 2 000 mg/kg bw.

Under the conditions of the study, the acute oral LD50 value of the test item was found to be above 2 000 mg/kg bw in female CRL: (WI) rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study was performed in accordance with standardised guidelines and under GLP conditions. The study was assigned a reliability score of 1 in line with the principles for assessing data quality as defined by Klimisch et al. (1997). The quality of the database is therefore considered to be good.

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

The acute oral toxicity of the test material was assessed in the female CRL: (WI) rat in accordance with the standardised guidelines OECD 423 and EU Method B.1 tris under GLP conditions.

Two groups of three female Crl: (WI) rats were treated with the test item at a dose level of 2000 mg/kg bw via oral gavage (Group 1 and Group 2).

A single oral treatment was carried out by gavage for each animal after an overnight food withdrawal. Food was made available again 3 hours after the treatment. The test item was administered formulated in Distilled water at a concentration of 200 mg/mL at a dose volume of 10 mL/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; therefore no further testing was required.

Clinical observations were performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on Days 1, 0 and 7 and before necropsy. All animals were subjected to a necropsy and a macroscopic examination.

The test material did not cause mortality at a dose level of 2000 mg/kg bw. All animals were symptom free during the study. Body weight gains of test item-treated animals during the study showed no indication of a test item-related effect. There was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw.

Under the conditions of the study, the acute oral LD50 value of the test item was found to be above 2000 mg/kg bw in female CRL: (WI) rats

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to acute oral toxicity.