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Description of key information

Key study: Test method OECD 420. GLP study. No adverse effects were observed in rats after a single exposure of 2000 mg/k bw by gavage.

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:
7 October 2014 - 16 December 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test method according to OECD Guideline 420. GLP study.
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Experimental Medicine Centre at the Medical University in Białystok
- Age at study initiation: 11 week-old
- Weight at study initiation: average body weight: 225.8 g
- Fasting period before study: about 19 hours before the administration of the test item, restored 3 hours after the administration
- Housing: plastic cages covered with wire bar lids, 58 x 37 x 21 cm, with UV-sterilized wood shavings as bedding.
- Diet (e.g. ad libitum): ad libitum, "Murigran" standard granulated laboratory food.
- Water (e.g. ad libitum): ad libitum, tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24ºC
- Humidity (%): 40-85%
- Air changes (per hr): 16 times/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
Corn oil was introduced to a beaker containing 4000 mg of the test item to obtain a suspension in a volume of 10 mL. The oil suspension of the test item was prepared on the administration day (shortly before the administration).

MAXIMUM DOSE VOLUME APPLIED: 0.5 mL/100 g bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The starting dose for the sighting study was selected from the fixed dose levels of 5, 50, 300 and 2000 mg/kg bw. Since no data were available, the sighting study commenced with the administration of the test item at a dose of 300 mg/kg bw to one female rat. Considering the fact that no evident toxicity was produced, the test item at a single dose of 2000 mg/kg bw was administered to the next animal. Since no effects were observed during the 14 days observation period, the dose of 2000 mg/kg bw was selected to be used in the main study.
Doses:
Sighting study: 300 and 2000 mg/kg bw
Main study: 2000 mg/kg bw
No. of animals per sex per dose:
2 female in the sighting study.
4 females in the main study.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on days 0 (directly before the administration of the test item), 7, and 14 (before euthanasia).
- Necropsy of survivors performed: yes
- Other examinations performed:
General condition: observation of all animals for morbidity and mortality: twice a day or once a day (on days off) during the 14-day experiment.
Detailed clinical observations: on the day of the test item administration (day 0), i.e. 10, 30, and 60 minutes after the administration and then at hourly intervals up to the 5th hour after the administration. From the 1st to the 14th day of the experiment, the detailed clinical observations were performed once a day.
Gross examinations: After the 14-day observation period, all animals were euthanized by intraperitoneal administration of morbital at a dose of 200 mg/kg bw and subjected to gross examinations. The detailed gross examinations comprised the observation of the external body surface, all natural apertures, and the cranial, thoracic, and abdominal cavities with their contents.
Preliminary study:
Clinical signs: No signs of toxicity were found. The animal survived the experiment.
Body weight: During the 14-day experiment, body weight gain was found in all animals.
Gross examinations: No lesions were found in the animals.
Sex:
female
Dose descriptor:
discriminating dose
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived the experiment.
Clinical signs:
No signs of toxicity were found.
Body weight:
During the 14-day experiment, body weight gain was found in all animals.
Gross pathology:
No lesions were found in the animal.
Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
No adverse effects were observed in rats after a single exposure of 2000 mg/k bw by gavage.
Executive summary:
The acute oral toxicity study based on a fixed dose method was performed according to OECD Guideline 420 (GLP study). The experiment commenced with a sighting study in which the test item at a single dose of 300 and 2000 mg/kg bw was administered to each female rat respectively. Considering the fact that no sign of toxicity was found in the sighting study, four animals used in the main study were given the test item at a dose of 2000 mg/kg bw. After the administration of the test item, the animals were observed for 14 days. General and detailed clinical observations were conducted daily during the entire experiment. Body weights of the animals were determined. After the 14-day observation period, the animals were euthanized and subjected to a necropsy and a detailed gross examination. No signs of toxicity were found and all animals survived the experiment. During the 14-day experiment, body weight gain was found in the animals. Regarding the gross examinations, no lesions were found in the animals. No adverse effects were observed in rats after a single exposure of 2000 mg/k bw by gavage.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Klimisch score = 1. GLP study.

Additional information

Key study: The acute oral toxicity study based on a fixed dose method was performed according to OECD Guideline 420 (GLP study). On the grounds of the sighting study results (two rats exposed to 300 and 2000 mg/kg bw respectively), four animals used in the main study were given the test item at a dose of 2000 mg/kg bw. After the administration of the test item, the animals were observed for 14 days. No signs of toxicity were found. The animal survived the experiment. Gross examination did not reveal any pathological changes in the examined animals.


Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for classification or non-classification

Based on the available results, the substance is not classified for acute toxicity according to CLP Regulation (EC) no. 1272/2008.