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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 Jan. 2019 - 22. Mar. 2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2019

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Slovak Academy of Sciences Dobrá Voda, Slovak Republic
- Age at study initiation: 8-9 weeks; female animals were non-pregnant and nulliparous
- Animal Health: Health condition of animals was examined by a veterinarian before initiation of the study.

ENVIRONMENTAL CONDITIONS
The animals were housed in plastic cages suspended on stainless steel racks, 3 animals per cage in a room equipped with central air conditioning. The average room temperature was maintained within the range of 22.12 ± 0.24 °C, relative humidity within 54.92 ± 2.46 %. The light regimen was set to a 12-hour light /12-hour dark cycle. Sanitation was performed according to the standard operation procedures. The laboratory food ssniff (ssniff Spezialdiäten GmbH, Germany) was available ad libitum. The animals received tap water for human consumption. Supply of drinking water was unlimited. The quality of drinking water is periodically analysed and recorded.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
The required amount of the test item (according to the body weight and dose) was mixed with vehicle (Olive oil) shortly before administration. The dose of 2000 mg/kg was administered in a volume of 5 mL/kg body weight.

ADMINISTRATION:
The test item was administered in a single dose by gavage using a metal stomach tube. Animals were fasted 10-12 h prior to dosing (food but not water was withheld over-night). Following a period of fasting, animals were weighed and the test item administered. After test item administration, food was withheld for further 3-4 hours.
Doses:
2000 mg/kg bw.
No. of animals per sex per dose:
3 females per treatment step.
Control animals:
no
Details on study design:
Clinical Observation
Animals were observed individually immediately after administration of the test item and 0.5, 1, 2, and 4 hours later. Each animal was inspected daily for the next 14 days.

Body Weight
Individual weights of animals were measured immediately prior to administration of the test item and weekly thereafter. Weight differences after first and second weeks after administration were calculated and recorded.

Necropsy
All test animals were subjected to gross necropsy and the results were recorded for each animal. Examinations included: external body surface and orifices, the appearance of tissues and organs in the thoracic cavity (trachea, esophagus, heart, aorta, lungs with main stem bronchi, thymus, tracheobronchial lymph node) and in the abdominal cavity (liver, spleen, adrenal glands, kidneys, ovaries, uterus including cervix, urinary bladder, small intestine, large intestine, pancreas, stomach, mesenteric lymph nodes).

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed during the study.
Clinical signs:
During the follow up period, no animals displayed signs of intoxication, change of health, nor any other adverse reaction.
Body weight:
At the end of the study the body weights of all animals were higher than the initial body weights. A slight decrease of body weights in animals No 1 and No 2 was observed between the first and second week after administration of the test item.
Gross pathology:
All animals were necropsied. During necropsy, no macroscopic findings were observed.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
All validity criteria are fulfilled. The study can be considered as valid. Under the study conditions, the oral LD50 of the test substance was considered to be >2,000 mg/kg bw in rats. Therefore, the test substance is not classified as toxic by oral route according to the criteria of EU CLP Regulation (1272/2008/EEC).
Executive summary:

The purpose of the study was to evaluate the potential toxic effect of the test item “Bisamid” when administered as a single oral dose to Wistar rats. The procedure according to OECD Guideline 423 Acute Toxic Class (ATC) method was used. A limit dose of 2000 mg/kg body weight was used as a starting dose. The test item administered to 6 females at a limit dose did not cause death. No signs of toxicity were observed during the first 4 hours in females or the 14-day observation period thereafter. At the end of the study the body weights of all animals were higher than the initial body weights. A slight decrease of body weights in two animals was observed between the first and second week after administration of the test item. During necropsy, no macroscopic findings were observed. The LD50 of the test item “Bisamid” is greater than 2000 mg/kg body weight after single oral administration to Wistar rats. Therefore, the test substance is not classified as toxic by oral route according to the criteria of EU CLP Regulation (1272/2008/EEC).


Route: .live1