[No public or meaningful name is available]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 JUL 2020 - 27 OCT 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Testing Guidelines for Studies of Chemicals, Chapter 5 Health impact test field, Section 18 Acute Oral toxicity - Acute Toxic Class Method

Version / remarks:

Notification No. 2019-23, National Institute of Environmental Research, Republic of Korea
(Jun. 13, 2019)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

Adopted: 17th December 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

bis(2,2,6,6-tetramethyl-1-(1,3-benzothiazol-2-ylsulfanyl)piperidin-4-yl)carbonate

Cas Number:

2311845-49-3

Molecular formula:

C33H42N4O3S4

IUPAC Name:

bis(2,2,6,6-tetramethyl-1-(1,3-benzothiazol-2-ylsulfanyl)piperidin-4-yl)carbonate

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Young Bio Co., Ltd.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9 weeks
- Weight at study initiation: 194.9 - 211.6 g
- Housing: Animals were individually identified on the tail by permanent markers, red in the acclimation period, and blue in the test period. Identification cards including information such as study number, test substance name, sex, animal number, experimental period and study director were attached to each cage.
- Diet (e.g. ad libitum): Radiation-sterilized animal feed for rats, 1314 IRR [Altromin Spezialfutter GmbH & Co. KG (Im Seelenkamp 20, D-32791 Lage Postfach 11 20, D-32770 Lage_Germany)] was given ad libitum, and the contamination identification was confirmed by receiving a report from the manufacturer.
- Water (e.g. ad libitum): Tap water was filtered and sterilized by ultrasonic sterilizer and microfiltration device and was given ad libitum in 500 mL polycarbonate water bottles. The water was periodically analyzed in accordance with SOP of CentralBio Co., Ltd.
- Acclimation period: Upon receipt, all animals were kept in quarantine and acclimatized for 7 days for 1st group, 10 days for 2nd group, 14 days for 3rd group and 17 days for 4th group, respectively under the environment of the animal room of Non-Clinical Center, CentralBio Co., Ltd. During this period, all animals were observed daily for any signs of disease and only selected healthy animals were used in the study.
- Method of randomisation in assigning animals to test and control groups: Following the quarantine-acclimation period, selected healthy animals were randomly grouped based on body weights. The evenness for the average and standard deviation of body weights per group was checked during the group assignment. The animals were fasted for over-night(about 16 hours) and orally administered once by gavage using a stomach tube (sonde). Feed was provided approximately 4 hours after the administration.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):19.2-23.0 °C
- Humidity (%): 46.9 - 64.8 %
- Air changes (per hr): 10 - 15/hr
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

Storage conditions : Room temperature (1 - 30 °C) Expiration date : 2021. 06. 23.(Vehicle test), 2021.07.27. (1st step); 2021.08.07. (2nd-4th step) Manufacturer : DAEJUNG CHEMICALS & METALS Co., Ltd.

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30, 200 mg/mL
- Amount of vehicle (if gavage): The vehicle was added to 0.3 g of the test substance, and the total volume was adjusted to 10 mL.
- Justification for choice of vehicle: As the test substance is insoluble in water, corn oil was used in the vehicle test in accordance with OECD TG 423, and the test substance was suspended in corn oil. As a result, corn oil was selected as an appropriate vehicle as it would ease the test substance administration and have no effect on the test system.
- Lot/batch no. (if required): C3311UC1 (Vehicle test), C3311UF1 (1st-4th step)

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The starting dose level was selected as 300 mg/kg body weight (bw) due to a lack of toxicity information of the test substance.

Doses:

300 and 2000 mg/kg; the dosing volume was 10 mL/kg bw and was calculated on the basis of fasted body weight on the administration day.

No. of animals per sex per dose:

3

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Day 3, Day 7, and Day 14
- Necropsy of survivors performed: yes
- Clinical signs including body weight: observed on Day 3, Day 7, and Day 14
- Other examinations performed: clinical signs, body weight, necropsy

Statistics:

Statistical analysis was not performed

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed in this study.

Clinical signs:

diarrhoea

other:

Body weight:

other body weight observations

Remarks:

No body weight changes related to the test substance administration were observed in all animals in the 300 mg/kg bw (1st and 2nd step), and 2,000 mg/kg bw groups (3rd and 4th step).

Gross pathology:

No gross lesions related to the test substance administration were observed in all animals in
the 300 mg/kg bw (1st and 2nd step), and 2,000 mg/kg bw groups (3rd and 4th step).

Applicant's summary and conclusion

Interpretation of results:

other: EU GHS criteria not met

Conclusions:

The acute oral LD50 in rats for test item is shown to be greater than 2,000 mg/kg bw and the acute
oral LD50 is estimated to be greater than the cut-off value of 5,000 mg/kg bw based on the results.
According to the UN GHS's classification criteria for acute oral toxicity, the test substance was
"Unclassified or Category 5". Hence, the EU GHS criteria are not met.

Executive summary:

This Acute Oral Toxicity Study was performed in female Sprague-Dawley rats according to OECD guideline 423 under GLP compliance following the Acute Toxic class method. The purpose of this study was to determine the GHS category and LD50 cut-off value based on the acute toxicity of the test substance following a single oral administration to female Sprague-Dawley rats. The test substance was administered in a single dosing at a dose level of 300 mg/kg bw(1st and 2nd step) and 2,000 mg/kg bw (3rd and 4th step), respectively. Three animals were used for each step. Mortality, clinical signs and body weights were observed for 14 days and at the end of the 14-day observation period for each step, gross necropsy was performed. No mortality was observed in this study. In the 300 mg/kg bw group (2nd step), 2 animals (2/3) showed diarrhea at 1 hour after the test substance administration. For the remaining 14-day observation period, no clinical signs were observed in all animals. No clinical signs were observed in all animals in the 300 mg/kg bw (1st step), and 2,000 mg/kg bw groups (3rd and 4th step). No body weight changes related to the test substance administration were observed in all animals in the 300 mg/kg bw (1st and 2nd step), and 2,000 mg/kg bw groups (3rd and 4th step). No gross lesions related to the test substance administration were observed in all animals in the 300 mg/kg bw (1st and 2nd step), and 2,000 mg/kg bw groups (3rd and 4th step).

In conclusion, the acute oral LD50 in rats for the test substance is shown to be greater than 2,000 mg/kg bw and the acute oral LD50 is estimated to be greater than the cut-off value of 5,000 mg/kg bw based on the results of this study. According to the GHS's classification criteria for acute oral toxicity, the test substance was "Unclassified or Category 5".