Vinyl ethylene carbonate

Endpoint summary

Description of key information

Acute oral toxicity:

The acute oral LD50 cut off in rats for the test item was 300 mg/kg b.w.. 

 

Acute dermal toxicity:

The acute dermal LD₅₀ in rats for VEC was estimated to be more than 2000 mg/kg b.w. in female SD rats.

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:

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.

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

Specific details on test material used for the study:

Batch No.: A03-18-0081
Purity: ≥99.9%

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

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.

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:

other: 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

Gross pathology:

All animals under test showed no abnormalities at the gross necropsy.

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.)".

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

50 mg/kg bw

Quality of whole database:

Study performed to current OECD guidelines with no significant deviations and run in OECD GLP certified lab.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From August 09 to September 21, 2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Specific details on test material used for the study:

Batch No.: 10121040902
Purity: 99.92%

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rationale for alternative/additional species to rat (if applicable)
- Source: SPF (Beijing) Biotechnology Co., Ltd
- Females (if applicable) nulliparous and non-pregnant: yes
- Rationale for use of males (if applicable)
- Age at study initiation: 56 days on arrival, in the range of 63~77 days at the commencement of each animal’s dosing.
- Weight at study initiation: The body weight ranges were 222~235 g at arrival, the body weight ranges were 248~260 g at grouping.
- Fasting period before study:
- Housing: Animals were raised in suspended, stainless steel cages (L32.0 cm ×W60.0 cm×H20.0 cm) on cage racks (L199.0 cm×W70.0 cm×H171.0 cm). Animals were housed individually during the exposure period and returned to group-caging after that.
- Historical data:
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days
- Microbiological status when known
- Method of randomisation in assigning animals to test and control groups

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.8-24.9℃ (target value was 20-25℃)
- Humidity (%): 47-70% (target value was 40%-70%)
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): A controlled light cycle was 12 hours light, 12 hours dark.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk of the test animals, about 40 cm2.
- % coverage: 100%
- Type of wrap if used: The gauze was placed over the treatment area and was wrapped with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test item was removed by cotton wool soaked in water.
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

- 200 mg/kg bw
- 1000 mg/kg bw
- 2000 mg/kg bw

No. of animals per sex per dose:

Range-finding study: one female per dose
Main study: 2 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations were performed once during the first 30 minutes and at 1, 2, 4 and 6 hours after application approximately and then once each day for 14 days.
General observations were made once daily for the animals not been administrated with the test item.
Careful observations and records of animal fur changes, eyes and mucosa, respiratory, circulatory, nervous system, particularly limb activity and behavior changes were made. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhea, lethargy, sleep and coma.
Individual weights of animals were determined within 24 hours after arrival, at the end of adaption period, at grouping (the day before each animal's dosing day), on Day 0 (day of dosing), Day 7 and Day 14 or at death. Changes in weights were calculated and recorded.
- Necropsy of survivors performed:
Animals surviving to the end of the study were anesthetized by CO2 and bled by abdominal aorta to death. Their corpse treatments were entrusted to specialized agencies.
At the end of the test, a gross necropsy was performed on all animals under test. The necropsy included carefully eye examinations of the skin of the dorsal area, the abdominal, thoracic organs and their contents of all animals.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths or moribund status were found in all animals during the test.

Clinical signs:

other: No symptoms were found in all animals' administration skin during the test.

Body weight:

other body weight observations

Remarks:

The results indicated that all the body weight gains of animals showed a growing trend.

Gross pathology:

No abnormalities were found in all animals at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 in rats for VEC was estimated to be more than 2000 mg/kg b.w. in female SD rats.

Executive summary:

The study was performed to assess the acute dermal toxicity of VEC in Sprague Dawley rats. The method was designed to meet the OECD Guideline 402 under GLP.

The acute dermal LD₅₀ in rats for VEC was estimated to be more than 2000 mg/kg b.w. in female SD rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Study performed to current OECD guidelines with no significant deviations and run in OECD GLP certified lab.

Additional information

Acute oral toxicity:

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..

 

Acute dermal toxicity:

The study was performed to assess the acute dermal toxicity of VEC in Sprague Dawley rats. The method was designed to meet the OECD Guideline 402 under GLP.

The acute dermal LD₅₀ in rats for VEC was estimated to be more than 2000 mg/kg b.w. in female SD rats.

Justification for classification or non-classification

Oral: 50 mg/kg bodyweight < LD50 ≤ 300 mg/kg bodyweight (actual LD50 value: 50 - 300 mg/kg bodyweight);

Dermal: LD50 > 2000 mg/kg bodyweight.

Therefore in accordance with Regulation (EC) No. 1272/2008 (amended by 286/2011) Table 3.1.1, this substance should be classified as category 3 for Acute oral endpoint, and should not be classified for Acute dermal endpoint.

 

Specific target organ toxicity-single exposure:

No significant non-lethal toxic effects observed in acute oral and dermal toxicity study.

Therefore in accordance with Regulation (EC) No. 1272/2008 Table 3.8.1, this substance should not be classified for this endpoint.