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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2019-05-05 to 2019-05-31
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed to current OECD guidelines with no significant deviations and run in OECD GLP certified lab.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Vinyl ethylene carbonate
EC Number:
700-261-7
Cas Number:
4427-96-7
Molecular formula:
C5H6O3
IUPAC Name:
Vinyl ethylene carbonate
Test material form:
liquid
Specific details on test material used for the study:
Batch No.: A03-18-0081
Purity: ≥99.9%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Beijing Huafukang Biological Technology Co., Ltd.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: About 9 - 10 weeks when arriving this study system and the ages were in the range of 63 - 70 days at the commencement of each animal’s dosing.
- Weight at study initiation: About 199 - 243 g when arriving this study system. The body weight ranges were 191 - 240g at the commencement of dosing. Each animal's weight fell in an interval within ±20% of the mean body weights of any previously dosed animals at dosing.
- Fasting period before study: Diet and water was available to the animals ad libitum during test. Food was removed overnight prior to dosing and returned approximately three to four hours after dosing.
- Housing: housed in the facility's barrier system. Animals were raised in suspended, stainless steel cages (L32.0 cm × W28.0 cm×H20.0 cm) on cage racks (L167.0 cm × W70.0 cm × H171.0 cm). There were 10 cages per layer, and 4 layers per rack. Animals were housed individually during the test.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: All animals' physical check-up and acclimation had been finished at their original studies for more than 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.7-23.7 °C (target value 20 – 25 °C)
- Humidity (%): 41%-63% (target value 40% - 70%)
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE: Purified water (produced by HT-RO1000 purity system)

CLASS METHOD
- Rationale for the selection of the starting dose: According to OECD Guideline for Testing of Chemicals “Acute Oral Toxicity-Acute Toxic Class Method” (TG 423, adopted 2001), the dosing level of 300mg/kg b.w. was selected as the starting dose from one of four fixed dose levels (5, 50, 300 and 2000 mg/kg), and 3 animals will be used in each step.
Doses:
300, 2000, 300, 50, 50 mg/kg b.w.
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of Clinical Observations: Clinical observations were performed once during the first 30 minutes and at approximately 1, 2 and 4 hours after application approximately, and then once each day for up to 14 days. General observations were made once daily for the animals which have not been administrated with the test item.
- Necropsy of survivors performed: yes, animals surviving to the end of the study were anesthetized by CO2 and bled by abdominal aorta to death. A gross necropsy was performed on all animals under test. The necropsy included carefully eye examinations of the abdominal, thoracic organs and their contents of all animals.
- Other examinations performed:
- Body Weights: Individual weights of animals were determined within 24 hours (same day as grouping day) after arrival, on Day 0 (day of dosing), Day 7 and Day 14. The bodyweights of died animals were weighed during the test. At the end of the test surviving animals were weighed.
- Moribund or Mortality Inspection: Inspections were made twice daily, morning and afternoon, during normal working days (except that it was made once in the dosing and necropsy days), and once daily at weekends and public holidays.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
300 mg/kg bw
Based on:
test mat.
Mortality:
Dose Level (300 mg/kg b.w.) for the first time dosing: The Mortality is 0/3.
Dose Level (2000 mg/kg b.w.) for the second dosing: The Mortality is 3/3.
Dose Level (300 mg/kg b.w.) for the third dosing: The Mortality is 2/3.
Dose Level (50 mg/kg b.w.) for the fourth dosing: The Mortality is 0/3.
Dose Level (50 mg/kg b.w.) for the fifth dosing: The Mortality is 0/3.
Clinical signs:
Dose Level (300 mg/kg b.w.) for the first time dosing: All animals didn't show any abnormal symptoms at the 0.5, 1, 2 and 4 hours approximately after dosing.
Dose Level (2000 mg/kg b.w.) for the second dosing: All animals didn't show any abnormal symptoms at the 0.5, 1, 2 and 4 hours approximately after dosing.
Dose Level (300 mg/kg b.w.) for the third dosing: All animals didn't show any abnormal symptoms at the 0.5, 1 and 2 hours after dosing. At the 4 hours after dosing, animal 2302 died and animal 2301 showed low autogenic movement until died at the 5 hours after dosing.
Dose Level (50 mg/kg b.w.) for the fourth dosing: All animals didn't show any abnormal symptoms at the 0.5, 1, 2 and 4 hours approximately after dosing.
Dose Level (50 mg/kg b.w.) for the fifth dosing: All animals didn't show any abnormal symptoms at the 0.5, 1, 2 and 4 hours approximately after dosing.
Body weight:
All survival animals gained body weights at the first week after dosing and gained slowly or decreased body weights at the second week after dosing during test.
Gross pathology:
All animals under test showed no abnormalities at the gross necropsy.

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The acute oral LD50 cut off in rats for the test item was 300 mg/kg b.w.. According to the GHS's classification criteria for acute oral toxicity, the test item was classified as "Category 3 (50 - 300 mg/kg b.w.)".
Executive summary:

The study was performed to assess the acute oral toxicity of the test item in Sprague Dawley rats according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).

The test item was tested using a stepwise procedure and three female animals were used each group. The first step dosing was 300 mg/kg b.w.. Clinical observations and body weights were monitored during the study. All animals under test were subjected to a gross necropsy at the end of the study.

 

Dose Level (300 mg/kg b.w.) for the first time dosing: All animals didn't show any abnormal symptoms at the 0.5, 1, 2 and 4 hours approximately after dosing. The Mortality is 0/3.

Dose Level (2000 mg/kg b.w.) for the second dosing: All animals didn't show any abnormal symptoms at the 0.5, 1, 2 and 4 hours approximately after dosing. The Mortality is 3/3.

Dose Level (300 mg/kg b.w.) for the third dosing: All animals didn't show any abnormal symptoms at the 0.5, 1 and 2 hours after dosing. At the 4 hours after dosing, animal 2302 died and animal 2301 showed low autogenic movement until died at the 5 hours after dosing. The Mortality is 2/3.

Dose Level (50 mg/kg b.w.) for the fourth dosing: All animals didn't show any abnormal symptoms at the 0.5, 1, 2 and 4 hours approximately after dosing. The Mortality is 0/3.

Dose Level (50 mg/kg b.w.) for the fifth dosing: All animals didn't show any abnormal symptoms at the 0.5, 1, 2 and 4 hours approximately after dosing. The Mortality is 0/3.

 

Based on above results, the acute oral LD50 cut off in rats for the test item was 300 mg/kg b.w.. According to the GHS's classification criteria for acute oral toxicity, the test item was classified as "Category 3 (50 - 300 mg/kg b.w.)".