Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2019-03-26 to 2019-06-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
other: “Regulation on Test Methods for Chemical Substances” Notification No. 2018-12, National Institute of Environmental Research, Republic of Korea (Apr. 9, 2018)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

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

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
(Crl:CD(SD)), SPF
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: ORIENTBIO INC., Republic of Korea
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 7 weeks old
- Weight at study initiation: 189.7 - 197.0 g
- Fasting period before study: ca. 16 hours prior to dosing
- Housing: Stainless wire mesh cage, 260W×350D×210H (mm), One animal/cage (during the study)
- Diet (ad libitum): Pelleted rodent chow (Teklad Certified Irradiated Global 18 % Protein Rodent Diet 2918C) provided 4 hours post dosing
- Water (ad libitum): filtered and irradiated with UV light public tap water
- Acclimation period: 4 days quarantine and 3 days acclimation

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.2 - 22.3
- Humidity (%): 46.4 - 55.5
- Air changes (per hr): 10 − 15 clean, fresh, filtered air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle, light intensity: 150 − 300 Lux

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Lot no.: MKCG3257

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg

DOSAGE PREPARATION: The required amount of the test substance was weighed on an electronic balance and placed in a glass bottle. A small amount of vehicle, corn oil, was added and mixed using a vortex mixer until dissolved. The vehicle was gradually added to yield the desired concentration. All preparations were conducted just prior to use.

CLASS METHOD
- Rationale for the selection of the starting dose: IDue to the low expected toxicity of the test substance, 2,000 mg/kg was selected as the starting dose for this study
Doses:
Groups 1 and 2 (Steps 1 and 2): 2,000 mg/kg of the test substance
Steps 1−2: A dose of 2,000 mg/kg was administered and no mortality was observed (Step 1). A second dose of 2,000 mg/kg was administered. Again, no mortality was observed (Step 2).
No. of animals per sex per dose:
3 females/group, two steps
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations - at 30 minutes after dosing and at 1, 2, 4 and 6 hours after dosing on Day 0 and once daily thereafter for 14 days; weighing - prior to dosing on Day 0 and on Days 1, 3, 7 and on the day of necropsy (Day 14)
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 5 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths of animals at 2000 mg/kg throughout the study.
Clinical signs:
Abnormal gait was observed in 2 animals at 2000 mg/kg at 6 hours after dosing. Mucous stool was observed in 4 animals on Day 1, and they disappeared on Day 2.
Body weight:
Normal body weight gain was observed in all animals at 2000 mg/kg throughout the study.
Gross pathology:
No grossly visible findings were observed in any animal at 2000 mg/kg.

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 median lethal dose derived for the test substance was LD50 ≥ 5000 mg/kg bw.
Executive summary:

A study was performed to assess the acute oral toxicity of the test item following a single oral administration to the Sprague-Dawley (Crl:CD(SD)) female rats. The test was performed according to OECD 423 "Acute Oral Toxicity - Acute Toxic Class Method", EU Method B1 tris and “Regulation on Test Methods for Chemical Substances” Notification No. 2018-12, National Institute of Environmental Research, Republic of Korea (Apr. 9, 2018). 2000 mg/kg bw was selected as the starting dose. A group of three fasted females was treated with the starting dose. This was followed by another group of three fasted females at the same dose level. The test item was administered orally via gastric intubation, diluted in corn oil. The animals were observed 30 min, 1, 2, 4 and 6 hours after dosing and then once daily for fourteen days. Bodyweights were recorded on the day of dosing and on Days 1, 3, 7 and 14. At the end of the observation period all animals were anesthetized with CO2 and exsanguinated from the abdominal aorta and subjected to complete gross necropsy. There were no deaths during the study. Abnormal gait was observed in 2 animals at 2,000 mg/kg at 6 hours after dosing. Mucous stool was observed in 4 animals on Day 1, and they disappeared on Day 2. No other adverse clinical signs were noted. All animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy. The acute oral LD50 of the test item in the Sprague-Dawley rat, was estimated as being greater than 5000 mg/kg bw as no mortalities were noted in animals treated with 2000 mg/kg bw.