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Administrative data

Description of key information

Key study: OECD 420. GLP study. Based on the evident toxicity observed in rats after a single exposure of 300 mg/k bw by gavage, the substance is classified as category 4 according to CLP Regulation (EC) no. 1272/2008.

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 November 2013 - 30 November 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test method according to OECD Guideline 420. GLP study.
Reference:
Composition 0
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
Test material information:
Composition 1
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: 12 week-old
- Weight at study initiation: average body weight: 210.8 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): 20-23ºC
- Humidity (%): 32-55%
- 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
- Concentration in vehicle: 60 mg/mL
- Amount of vehicle (if gavage): 1 mL

MAXIMUM DOSE VOLUME APPLIED: 0.5 mL/100 g bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The test item at a single dose of 300 mg/kg bw was administered to one animal. The starting dose for the sighting study was selected from the fixed dose levels of 5, 50, 300 and 2000 mg/kg bw as a dose expected to produce evident toxicity. Since no data was 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 the evident toxicity was observed during the sighting study, the test item at a single dose of 300 mg/kg bw was administered to four animals. The animal from the sighting study which had received the dose of 300 mg/kg bw was included in the main study.
Doses:
Sighting study: 300 mg/kg bw
Main study: 300 mg/kg bw
No. of animals per sex per dose:
1 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: rounded back from the 30th minute to the 5th hour after the administration of the test item, wavering gait from the 30th minute to the 2nd hour, a distinct increase in locomotor activity from the 30th minute to the 2nd hour, a slight increase in locomotor activity from the 3rd to the 5th hour, seizures from the 30th minute to the 2nd hour, and tremors from the 3rd to the 5th hour after the administration of the test item. It was difficult to catch the animal. Furthermore, strong reactions to sound stimuli were observed from the 30th minute to the 5th hour after the administration of the test item. This signs of toxicity were observed only on the administration day. The animal survived the experiment.
Body weight: During the second week of the experiment, body weight gain was stated. After the 14-day experiment, body weight gain was stated too.
Gross examinations: necrosis of the cecum, congestion around necrosis in the cecum, and petechiae in the mesentery of the cecum. These changes were probably caused by the test item.
Sex:
female
Dose descriptor:
discriminating dose
Effect level:
300 mg/kg bw
Based on:
test mat.
Remarks on result:
other: (evident toxicity)
Mortality:
All animals survived the experiment.
Clinical signs:
The following changes were observed in all animals: rounded backs from the 30th minute to the 4th hour after the administration of the test item, a distinct increase in locomotor activity from the 10th to the 30th minute, a slight increase in locomotor activity from the 1st to the 5th hour and on the 1st day after the administration of the test item, strong reactions to sound stimuli from the 10th minute to the 5th hour and on the 1st day after the administration of the test item, and accelerated respiration during the 10th minute after the administration of the test item. It was difficult to catch the animals. The following changes were observed in individual animals: tremors in animal no. 2 from the 1st to the 3rd hour after the administration of the test item and in animal no. 5 during the 2nd hour, seizures in animal no. 5 during the 1st hour, and a bristled coat in animal no. 2 during the 1st hour after the administration of the test item. This signs of toxicity were observed only on the administration day and the first day after administration.
Body weight:
During the 14-day experiment, body weight gain was stated in all animals.
Gross pathology:
The animals did not exhibit any pathological changes.
Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Key study: OECD 420. GLP study. Based on the evident toxicity observed in rats after a single exposure of 300 mg/k bw by gavage, the substance is classified as category 4 according to CLP Regulation (EC) no. 1272/2008.
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 mg/kg bw was administered to one female rat. Considering the fact that the evident toxicity was found during the sighting study, four animals used in the main study were given the test item at a dose of 300 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. Following single administration of the test item at a dose of 300 mg/kg bw to four animals used in the main study, rounded backs, distinct and slight increases in locomotor activity, strong reactions to sound stimuli, and accelerated respiration were stated in case of all animals. All animals were difficult to catch. Furthermore, a bristled coat, tremors, and seizures were noticed. This signs of toxicity were observed on the administration day and the first day after administration. All animals survived the experiment. During the first and the second weeks of the experiment, body weight gain was stated in all females used in the study. After the 14-day experiment, body weight gain was stated too. Gross examinations of rat no. 1 revealed necrosis of the cecum, congestion around necrosis in the cecum, and petechiae in the mesentery of the cecum. These changes were probably caused by the test item. The remaining animals did not exhibit any pathological changes. Considering the fact that the evident toxicity was stated at a dose 300 mg/kg bw the test item was classified to the categories 4 according to the CLP Regulation (EC) no 1272/2008.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
300 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). The experiment commenced with a sighting study in which the test item at a single dose of 300 mg/kg bw was administered to one female rat. Considering the fact that the evident toxicity was found during the sighting study, four animals used in the main study were given the test item at a dose of 300 mg/kg bw. After the administration of the test item, the animals were observed for 14 days. Evident toxicity (such clinical signs as tremors, seizures, changes in motor activity, hyperexcitability, accelerated respiration) was observed in rats. The substance was classified for category 4 according to the CLP Regulation (EC) no 1272/2008.


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

Justification for classification or non-classification

Based on the available results (evident toxicity at a dose 300 mg/kg bw), the substance is classified for Acute Toxicity Category 4 according to CLP Regulation (EC) no. 1272/2008.