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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:
2016-03-16 to 2016-07-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
Crl:CD (SD), SPF
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks old
- Weight at study initiation: 176.3-195.3 g
- Fasting period before study:animals were fasted overnight, approximately 16 hours prior to dosing
- Housing:cage in an animal room
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: for four days after three days of quarantine (including health examiniation)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5-24.0 °C (measured), permissible range 19-25 °C
- Humidity (%): 43.5-58-5% (measured) permissible range 30-70 %
- Air changes (per hr): 10-15 clean, fresh, filterd air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 500 mg/mL
- Lot/batch no. (if required): MKBS6944V

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: due to the low expected toxicity of the test substance a starting dose of 5,000 mg/kg was selected.
Doses:
Step 1: starting dose of 5,000 mg/kg test substance was administered to one animal
Step 2: two animals were administered the test substance at 5,000 mg/kg, because there was no dead animal at 5,000 mg/kg (step 1)
No. of animals per sex per dose:
Step 1 : 1 animal
Step 2: 2 animals
Control animals:
no
Details on study design:
- Duration of observation period following administration:14 days
- Frequency of observations and weighing: observations for mortality, clinical signs, general conditions at 30 minutes after dosing and at 1,2,4,6 hours after dosing on day 0 and once daily thereafter for 14 days; body weight was recorded prior to dosing on day 0 and on day 1, 3,7, and on day of necropsy, day 14
- Necropsy of survivors performed: yes
- Other examinations performed: no histopathology, since no gross findings were obsereved at necropsy.
Statistics:
Statistical analysis was not performed. Mean scores and values are determined.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals at 5,000 mg/kg survived the duration of the study. There were no effects on the mortality. Refer to Table 1.
Clinical signs:
Mucous stool was observed in one animal at 5,000 mg/kg on Day 1 after dosing and it disappeared on Day 2 after dosing. Therefore, it was considered to be a test substance-related temporary change. Refer to table 2.
Body weight:
A tendency to supress body weight gain was observed in all animanls on Day 1 after dosing at 5,000 mg/kg. These animals returned to normal on day 3. This change was considered to be a test substance-related effect. Refer to table 3 and 4.
Gross pathology:
No gross visible evidence of morphological abnormalities was observed in any animal at 5,000 mg/kg.

Any other information on results incl. tables

Table 1: Summary of Mortality

Step / Dose (mg/kg)

No. of animals

Days after dosing

Mortality

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Step 1/ 5,000

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0/1

Step 2/ 5,000

2

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0/2

 

Table 2: Individual Clinical Signs

Step / Dose (mg/kg)

Animal ID

Clinical sign

Hours (Day 0) after dosing

0.5

1

2

4

6

Step 1/ 5,000

2101

 

-

-

-

-

-

Step 2/ 5,000

2201

 

-

-

-

-

-

2202

 

-

-

-

-

-

 

Step / Dose (mg/kg)

Animal ID

Clinical sign

Days after dosing

 

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Step 1/ 5,000

2101

 

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Step 2/ 5,000

2201

 

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

 

2202

Mucous stool

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-: No observable abnormality

+: Observable abnormality

Table 3. Individual Body Weights

Step/Dose (mg/kg)

Animal ID

Days after dosing

Gain

0 ~ 14

0

1

3

7

14

 

 

 

 

 

 

 

 

Step 1

5,000

2101

176.3

185.9

202.0

212.9

234.9

58.6

Step 2

5,000

2201

184.6

193.8

213.4

223.8

227.5

42.9

2202

195.3

198.9

214.1

228.6

235.5

40.2

 

Mean

190.0

196.4

213.8

226.2

231.5

41.6

S.D.

7.6

3.6

0.5

3.4

5.7

1.9

N

2

2

2

2

2

2

 

 

Table 4. Individual Body Weights during an Acclimation Period

Animal ID

Temporary Animal ID

Receipt

Group assignment

2101

2002

170.9

198.0

2201

2202

2001

174.3

192.5

2004

180.4

204.4

2003

183.9

211.3

 

Mean

177.4

201.6

S.D.

5.9

8.1

N

4

4

 

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the result of the acute oral toxicity study in Sprague-dawley rats, the test substance has an LD50 value >5000 mg/kg bw. Therefore, it was not classified according to CLP.
Executive summary:

The purpose of this study was to assess the potential toxicity of the test substance following a single oral dose administration to female Sprague-Dawley rats and to classify the test substance under GHS classification.

 

Two dose groups were designed as Steps 1 and 2 at 5,000 mg/kg. Step 1 consisted of one female and Step 2 consisted of two females. All animals were monitored for clinical signs and body weight changes during the 14-day observation period after administration. They were subjected to gross necropsy at the end of the observation period.

 

There were no deaths of animals at 5,000 mg/kg. Mucous stool was observed in an animal on Day 1 after dosing and it disappeared on Day 2 after dosing. A tendency to suppress body weight gain was observed in animals on Day 1 after dosing. Then, these animals returned to normal on Day 3. No test substance-related effects were observed in the necropsy in any animal.

 

Based on the result of the acute oral toxicity study in Sprague-Dawley rats, the test substance was not classified according to the GHS classification and the median lethal dose derived was: LD50 cut off> 5,000 mg/kg b.w.