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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From July 26 to August 31, 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
2001
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
2008
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
no

Test material

Constituent 1
Reference substance name:
Intercure 18
IUPAC Name:
Intercure 18
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: body weight variation did not exceed ± 20 % of the mean body weight
- Fasting period before study: overnight fast immediately before dosing
- Housing: The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet: 2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK ad libitum):
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30 to 70 %
- Air changes (per hr): fifteen changes
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
SIGHTING TEST
Using available information on the toxicity of the test item, 300 mg/kg was chosen as the starting dose.
A single animal was treated as follows:
Dose Level (mg/kg)= 300
Concentration (mg/mL) = 30
Dose Volume (mL/kg) = 10
Number of Rats (Female) = 1

In the absence of toxicity at a dose level of 300 mg/kg, an additional animal was treated as follows:
Dose Level (mg/kg)= 2000
Concentration (mg/mL) = 200
Dose Volume (mL/kg) = 10
Number of Rats (Female) = 1


MAIN STUDY
Due to mortality and signs of systemic toxicity at a dose level of 2000 mg/kg, an additional group of animals was treated as follows:
Dose Level (mg/kg)= 300
Concentration (mg/mL) = 30
Dose Volume (mL/kg) = 10
Number of Rats (Female) = 4
Doses:
SIGHTING TEST: 300 mg/kg, 2000 mg/kg
MAIN STUDY: 300 mg/kg
No. of animals per sex per dose:
300 mg/kg (1animal during Sighting Test)
2000 mg/kg (1 animal during Sighting Test)
300 mg/kg (4 animals during Main test)
Control animals:
no
Details on study design:
All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose group to confirm the survival of the previously dosed animals.
Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for up to 14 days. Morbidity and mortality checks were made twice daily.
Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14 or at death.
At the end of the observation period the surviving animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The animal treated at a dose level of 2000 mg/kg was found dead 1 day after dosing. There were no deaths at a dose level of 300 mg/kg.
Clinical signs:
Hunched posture was noted 2 and 4 hours after dosing in the animal treated at a dose level of 2000 mg/kg. There were no signs of systemic toxicity at a dose level of 300 mg/kg
Body weight:
Surviving animals showed expected gains in body weight.
Gross pathology:
Abnormalities noted at necropsy of the animal treated at a dose level of 2000 mg/kg were abnormally red lungs, dark liver, dark kidneys and white material present in the stomach. No abnormalities were noted at necropsy of animals treated at a dose level of 300 mg/kg.

Applicant's summary and conclusion

Interpretation of results:
other: Category 4 According to the CLP Criteria
Conclusions:
The LD50 of the test substance is in a range of 300 - 2000 mg/kg bw.
Executive summary:

Method

The study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat, according to the OECD guideline 420.

Following a sighting test at dose levels of 2000 mg/kg and 300 mg/kg, a further group of four fasted females was given a single oral dose of test item, as a suspension in arachis oil BP, at a dose level of 300 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Results

Mortality. The animal treated at a dose level of 2000 mg/kg was found dead 1 day after dosing. There were no deaths at a dose level of 300 mg/kg.

Clinical Observations. Hunched posture was noted 2 and 4 hours after dosing in the animal treated at a dose level of 2000 mg/kg. There were no signs of systemic toxicity at a dose level of 300 mg/kg.

Body Weight. Surviving animals showed expected gains in body weight.

Necropsy. Abnormalities noted at necropsy of the animal treated at a dose level of 2000 mg/kg were abnormally red lungs, dark liver, dark kidneys and white material present in the stomach. No abnormalities were noted at necropsy of animals treated at a dose level of 300 mg/kg bw.

Conclusion

The LD50 of the test substance is in a range of 300 - 2000 mg/kg bw.

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