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Description of key information

No mortality was observed in 6 female Sprague-Dawley rats in an acute oral toxicity study with the test substance, conducted in accordance with OECD TG 423 at a limit dose of 2000 mg/kg. The LD50 was therefore identified as

>2000 mg/kg p.o. and the median lethal dose derived was LD50 cut off ≥ 5,000 mg/kg b.w.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 May 2017 to 7 June 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
Adopted 17th December 2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
other: "Regulation on Test Methods for Chemical Substances" Notification No. 2017-4, National Institute of Environmental Research, Republic of Korea (Mar. 14, 2017)
Deviations:
not specified
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: ORIENTBIO INC., Republic of Korea
- Age at study initiation: 8 weeks
- Weight at study initiation: 183.0-185.1 g
- Fasting period before study: yes, animals were fasted overnight, approximately 16 hours prior to dosing
- Housing: one animal/ cage
- Diet (e.g. ad libitum): Pelleted rodent chow, ad libitum
- Water (e.g. ad libitum): Public tap water in Cheongju-si was filtered and irradiated by ultraviolet light and provided ad libitum.
- Acclimation period: 3 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1−23.2°C (Measured value)
- Humidity (%): 43.7 - 53.9 % (Measured value)
- Air changes (per hr): 10−15 clean, fresh, filtered air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle, 150 - 300 Lux

IN-LIFE DATES: From: To: 16 May - 2 June 2017
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 400 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg body weight

- Rationale for the selection of the starting dose: The starting dose of 2,000 mg/kg was selected due to the low expected toxicity of the test item.
Doses:
2000 mg/kg
No. of animals per sex per dose:
2 groups of 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for mortality, general condition and clinical signs 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 (Day 1−Day 14). The body weight was recorded 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
- Other examinations performed: complete gross postmortem examinations
Statistics:
Statistical analysis was not performed. Mean scores and values were determined.
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
>= 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities observed at 2000 mg/kg.
Clinical signs:
Abnormal gait was observed in 2−4 animals at 2000 mg/kg at 2−6 hours after dosing, and mucous stool was observed in all animals on Day 1. These signs 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.
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The test item was classified as Category 5 or Unclassified according to the GHS classification and the median lethal dose derived was: LD50 cut off ≥ 5,000 mg/kg b.w.
Executive summary:

The toxicity of test item following a single oral dose administration to female Sprague-Dawley rats was tested according to OECD 423 and EU B.1 tris guidelines.

All animals were monitored for clinical signs and body weight changes during the 14-day observation period after administration and a gross necropsy was performed at the end of the observation period.

There were no deaths of animals at 2000 mg/kg. Abnormal gait was observed in animals at 2000 mg/kg on the day of dosing and mucous stool was observed on Day 1. And they disappeared on Day 2. No test substance-related effects were observed in body weight data or necropsy findings in any animal at 2000 mg/kg. The test item was classified as Category 5 or Unclassified according to the GHS classification and the median lethal dose derived was: LD50 cut off ≥ 5,000 mg/kg b.w.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Reliable without restrictions
the actual LD50 was given as >2000 mg/kg b.w.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The acute oral toxicity of the test substance was evaluated in Sprague-Dawley rats.

None of the animals died after a single oral administration of 2000 mg/kg bw. Therefore, the LD50 p.o. rat is > 2000 mg/kg b.w. On the day of administration only,abnormal gait and mucous stool were observed in some animals. All signs had resolved by Day 2 and no alterations in the general state of well-being were observed in any animals during the further course of investigation. The body weight gain of the animals was not affected.


Justification for selection of acute toxicity – oral endpoint
According to REACH Annex VIII section 8.5, column 2, acute oral toxicity is required unless the substance is classified as corrosive

Justification for classification or non-classification

Based on the results of the acute oral toxicity studies , it can be concluded that the test substance has a very low toxicity to rats after a single oral administration. According to the current EU-CLP criteria, this compound cannot be classified with respect to its acute oral toxicity, as the LD50 values for this endpoint exceeds the range given for all four categories of the EU-CLP system. No risk phrase is required. Similarly, the test substance is also unclassified (Category 5) according to Regulation (EC) No 1272/2008 (2017) and the median lethal dose derived was LD50 (cut off) >/=5000 mg/kg bw.