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Description of key information

Acute Toxicity: Oral: LD50 > 2,000 mg/kg bw; OECD 423; Jae-Bum Na., 2018

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:
11 May - 20 July 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study conducted to international guideline and under GLP
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
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
Version / remarks:
2018
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Remarks:
(Crl:CD(SD)),SPF
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: ORIENTBIOINC.,RepublicofKorea
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: 163.4 - 196.9 g
- Fasting period before study: yes
- Housing: Animals were individually housed in Stainless wire mesh cage, 260W×350D×210H (mm), One animal/cage (during the study).
- Diet (e.g. ad libitum): Pelleted rodent chow
(Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C, Lot no. 2918C-012918MA) placed in feeders and provided ad libitum. 
- Water (e.g. ad libitum): Public tap water in Cheongju-si was filtered and irradiated by ultraviolet light and provided ad libitum. 

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.0−25.0°C
- Humidity (%): 30.0−70.0%
- Air changes (per hr): 10−15 clean, fresh, filtered air changes per hour
- Photoperiod (hrs dark / hrs light): 12 : 12
IN-LIFE DATES: 23/5/ 2018 - 12 and 15 June 2018
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Oral via gastric intubation
Details on oral exposure:
Individual doses were calculated based on the animals’ body weight recorded just prior to dosing at a dose volume of 10 mL/kg body weight. Animals were dosed via gastric intubation with a 3-mL disposable syringe fitted with an intubation tube. Animals were fasted overnight, approximately 16 hours prior to dosing. Drinking water was provided ad libitum. Feed was provided approximately 4 hours after dosing.
Doses:
2,000 mg/kg
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
Due to the low expected toxicity of the test substance, 2,000 mg/kg was selected as the starting dose. A dose of 2,000 mg/kg was administered to three females. Based on observation of no mortality,a second dose of 2,000 mg/kg was administered to another set of 3 female.
Statistics:
Not required but mean scores and values were determined.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No adverse effects observed
Mortality:
No deaths reported
Clinical signs:
Compound-colored stool was observed in all animals at 2,000 mg/kg on Day 1 after dosing. Then, these animals returned to a normal appearance on Day 2 after dosing.
Body weight:
Normal body weight gain was observed in all animals at 2,000 mg/kg throughout the study.
Gross pathology:
No grossly visible abnormalities were observed in any animal at 2,000 mg/kg.
Other findings:
None

Table 2. Mean Body Weights

Step / Dose(mg/kg)

Days after dosing

0

1

3

7

14

Gain (g)014

Step 1

 2,000

174.1

190.6

200.2

209.8

235.7

61.6

Step 1

 2,000

186.5

208.7

221.1

229.6

246.4

59.9

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System).
Executive summary:

OECD 423 (2018) - In an acute oral toxicity study, a group of  7-8 week old female Wistar rats were given a single oral dose of the test item using a stepwise dose rate of 2000 mg/kg bw and observed for 14 days.

In the absence of mortality during the observation period, the oral LD50 was estimated to be > 2000 mg/kg bw.

Compound-coloured stool was observed in animals on Day 1. This change disappeared on Day 2. No test substance-related effects were observed in the body weight data or necropsy findings in any animal at 2,000 mg/kg.

In conclusion, the test item did not meet the criteria for classification according to Regulation (EC) No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The endpoint is concluded based on a single key study with a Klimisch rating of 1. No effects were observed up to the limit dose of 2000 mg/kg bw/day

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

OECD 423 (2018) - In an acute oral toxicity study, a group of  7-8 week old female Wistar rats were given a single oral dose of the test item using a stepwise dose rate of 2000 mg/kg bw and observed for 14 days.

In the absence of mortality during the observation period, the oral LD50 was estimated to be greater than 2000 mg/kg bw.

Compound-coloured stool was observed in animals on Day 1. This change disappeared on Day 2. No test substance-related effects were observed in the body weight data or necropsy findings in any animal at 2,000 mg/kg.

In conclusion, the test item did not meet the criteria for classification according to Regulation (EC) No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

Justification for classification or non-classification

The test item did not meet the criteria for classification according to Regulation (EC) No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.