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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:
From 2017-11-21 to 2018-01-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report date:
2018

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
Adopted: 17th December 2001
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
Lot No.: C170806
Purity: 100 %

Test animals

Species:
rat
Strain:
other: Crl: CD(SD)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Orient Bio Co., Ltd.
- Age and weight at study initiation:
9 weeks old , 189.6 g - 191 .4 g (1st step)
10 weeks old , 192.7 g - 204.6 g (2nd step)
9 weeks old, 204.5 g - 210.7 g (3rd step)
10 weeks old , 209.0 g - 229.5 g (4th step)
- Fasting period before study: over-night (18 hours)
- Housing: Stainless steel wire cage, (310W x 5000 x 200H) mm, Less than 3 animals per cage
- Diet: Rodent Oiet 20 5053 [Labdiet, USA], ad libitum
- Water: R/O water, ad Iibitum
- Acclimation period: at least 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 .5 - 23.2
- Humidity (%): 48.7 - 62.8
- Air changes (per hr): 10-20 times/h
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Methyl cellulose : Sterile distilled water = 1g : 100 mL
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/mL (1st, 2nd step) , 200 mg/mL (3rd, 4th step)
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: This vehicle has been used widely in toxicity study. Before the study initiation date, this vehicle was chosen as appropriate vehicle of test substance preparation through the vehicle test.
- Lot/batch no. (if required): SLBR1658V for Methyl cellulose; A2R8B21, S1R9B21 for Sterile distilled water

DOSAGE PREPARATION:
Test substance was formulated with vehicle at 30 mg/mL (1st, 2nd step), 200 mg/mL (3rd, 4th step) concentration. The mixture of the test substance was homogenized by shaking. Each step of the preparation was conducted just prior to use.

CLASS METHOD
- Rationale for the selection of the starting dose: Based on LD50 of Material safety data sheet were 1710 and 2330 mg/kg for female and male rats separately. The starting dose level was 2000 mg/kg B.W in study plan. However, the document was wrongly written in preparation of test substance and dose level was changed to 300 mg/kg B.W. But this deviation is considered to be no effect on result of study.
Doses:
1st and 2nd step: 300 mg/kg B.W
3rd and 4th step: 2000 mg/kg B.W
No. of animals per sex per dose:
3 females for each
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs were carefully observed for 0.5, 1, 2, 3 and 4 hours after treatment and then once each day for 14 days.
Body weight were measured at animal receipt day, animal allocation day, just before treatment and on day 7 and 14 after the administration, found death animal.
- Necropsy of survivors performed: yes, At the end of observation period and death of animal, external observations were conducted and all survived animals were sacrificed by blood letting under anesthesia. Then the organs were examine for gross lesions.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The test substance-related dead animal was observed in 1 animal (on day 1) at 2000 mg/kg B.W. (3rd step).
Clinical signs:
There were no clinical signs caused by administration of the test substance.
Body weight:
For the results of body weight for animal except dead animal, 1 animal showed decreased body weight in 300 mg/kg B.W. (2nd step) on day 14 as compared with day 7. The other animals showed the normal increase of body weight during the study period.
Gross pathology:
In the necropsy finding of dead animal, hemorrhage in around mouth in external finding was observed in 1 animal at 2000 mg/kg B.W. (3rd step).
In the necropsy of surviving animals, there were no abnormal findings caused by administration of the test substance.

Applicant's summary and conclusion

Conclusions:
The LD50 was determined to be > 2000 mg/kg body weight.
Executive summary:

The present study, to investigate acute oral toxicity of the test item, was conducted on female Sprague-Dawley (SD) rats. An acute dose of the test substance was administered by oral route at a dose of 300 mg/kg B.W. (1st t, 2nd step) and 2000 mg/kg B.W. (3rd, 4th step). Three animals were used for each step and there were 4 steps in total.

- The test substance-related dead animal was observed in 1 animal at 2000 mg/kg B.W. (3rd step).

-There were no clinical signs caused by administration of the test substance.

- For the results of body weight for animal except dead animal, no test substance-related effects were observed.

- In the necropsy finding of dead animal, hemorrhage in around mouth in external finding was observed in 1 animal at 2000 mg/kg B.W. (3rd step).

In the necropsy of surviving animals, there were no abnormal findings caused by administration of the test substance.

The LD50 was determined to be > 2000 mg/kg body weight.