Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16.03.2016 - 06.07.2016
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: 7 weeks old
- Weight at study initiation: 170.9 - 183.9 g
- Fasting period before study: animals were fasted overnight, approximately 16 hours
- Housing: Stainless wire mesh cage (260W×350D×210H mm)
- Diet: ad libitum (starting approx. 4h after dosing), pelleted rodent chow (Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C)
- Water: ad libitum, public tap water
- Acclimation period: 4 days after 3 days of quarantine (including health examiniation)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5 - 24.0
- Humidity (%): 43.5 - 58-5
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 h light/12 h dark, 150-300 Lux

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:
5,000 mg/kg
No. of animals per sex per dose:
Step 1: 1
Step 2: 2
Control animals:
no
Details on study design:
- Duration of observation period following administration:14 days
- Frequency of observations and weighing: clinical signs daily and bodyweights on day 0, 1, 3, 7 and 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 survived, there were no effects on the mortality.
Clinical signs:
Mucous stool was observed in 1 animal on day 1 after dosing, however, it disappeared on day 2 after dosing. Therefore, it was considered to be a test substance-related temporary change.
Body weight:
A tendency to supress body weight gain was observed in all animals on day 1 after dosing. This returned to normal on day 3. This change was considered to be a test substance-related effect.
Gross pathology:
No grossly visible evidence of morphological abnormalities was observed in any animal.

Any other information on results incl. tables

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

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test item is considered not acute toxic and the LD50 > 5000 mg/kg bw.
Executive summary:

The purpose of the current study was to assess the potential toxicity of the test substance after a single oral administration. Acute oral dosing was performed according to OECD 423 and GLP.

Female Sprague-Dawley rats were allocated to groups at random. 1 animal was assigned to one group for the Step 1 and two animals were assigned to another group for Step 2. The animals of both dose groups (Steps 1 and 2) received 5000 mg/kg of the test item. 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.

No animals died during the study and thus there were no effects on the mortality.

In 1 animal mucous stool was observed on day 1 after dosing, however, it disappeared on day 2 after dosing.

Regarding the body weights of the animals, a tendency to suppress body weight gain was observed in all animals on day 1, however, it returned to normal on day 3. This change was considered to be a test substance-related effect.

During necropsy no grossly visible evidence of morphological abnormalities was observed in any animal.

Based on the result of the acute oral toxicity study in Sprague-Dawley rats, the test substance is not classified for acute oral toxicity and the median lethal dose derived was LD50 > 5000 mg/kg bw.