Ethylene carbonate

Endpoint summary

Description of key information

The LD50/LC50 values from the key-studies were: LD50 (oral, rat) 10400 mg/kg bw, LD50 (dermal, rat) > 2000 mg/kg bw, LC50 (inhalation, rat) > 730 mg/m3 air. The studies were performed respectively according to OECD guidelines 401, 402 and 403. 

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable with OECD Guideline 401 with acceptable restrictions (partly limited documentation, e.g. no details on test substance or concentration in vehicle; dose levels not clearly specified, no data on clinical signs or necropsy)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

see rationale for reliability

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Carworth-Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

Source: rats raised in the authors own colony
Diet: Rockland rat diet complete
Initial body weight: 90 to 120 g
Rats not fasted before dosing
No further data

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

No details

Doses:

dosages in a logarithmic series (no further data)

No. of animals per sex per dose:

Groups of five male rats

Control animals:

no

Details on study design:

Post exposure observation period 14 days

Statistics:

The LD50 value and its fiducial range are estimated by the method of Thompson (Bact. Rev. 11 :115, 1947) using the tables of Weil (Biometrics 8 :249, 1952).

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

10 400 mg/kg bw

95% CL:

7 940 - 13 620

Mortality:

no further data

Clinical signs:

other: no data

Gross pathology:

no data

Other findings:

no

Interpretation of results:

GHS criteria not met

Conclusions:

In male rats the LD50 is 10400 mg/kg bw.

Executive summary:

The study is comparable to OECD Guideline 401 with acceptable restrictions (partly limited documentation, e.g. no details on test substance or concentration in vehicle; dose levels not clearly specified, no data on clinical signs or necropsy).

Groups of 5 male Carworth-Wistar rats were gavaged with dosages in a logarithmic series. The post exposure observation period was 14 days. The authors calculated a LD50 value of 10400 mg/kg bw. The test substance is practically non-toxic.

Conclusion: In male rats the LD50 is 10400 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

10 400 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study is comparable with the inhalation hazard test described in the Annex of OECD Guideline 403 (adopted 1981) with acceptable restrictions (partly limited documentation; post exposure observation period 7 days; low number of rats)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

Annex of the Guideline 403

Deviations:

yes

Remarks:

see rationale for reliability

GLP compliance:

no

Test type:

other: inhalation hazard test

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

No details

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: air

Details on inhalation exposure:

Rats exposed for 8 h to a vapour saturated atmosphere.
Vapour was generated by bubbling 200 l/h dry air (no CO2) through the liquid substance column (volume ca. 50 ml) of about 5 cm above a fritted glass disc in a glass cylinder. The liquid had a temperature of 50°C; air pressure was 754 mm Hg. Temperature in the exposure chamber presumably 26°C (not clearly stated)

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

8 h

Concentrations:

Saturated vapour. The authors calculated a concentration of 730 mg/m³ (1.17 g substance loss).

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: observations performed (no details), body weight determined at day 0 and 4
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LC0

Effect level:

730 mg/m³ air

Exp. duration:

8 h

Remarks on result:

other: saturated vapour

Mortality:

No mortality

Clinical signs:

other: No clinical signs

Body weight:

No effects on body weight (measured day 0 and day 4)

Gross pathology:

No effects detected at necropsy

Other findings:

No

Interpretation of results:

GHS criteria not met

Conclusions:

No mortality in male and female rats exposed to saturated vapour for 8 h.

Executive summary:

The study is comparable to the inhalation hazard test described in the Annex of OECD Guideline 403 (adopted 1981) with acceptable restrictions (partly limited documentation; post exposure observation period 7 days; low number of rats).

Three male and 3 female rats were exposed for 8 h to saturated vapour. The authors calculated a concentration of 730 mg/m³. No clinical signs were observed and no mortality occurred during the 7 days of post exposure observation period. No effects were detected at necropsy.

Conclusion: No mortality in male and female rats exposed to saturated vapour for 8 h.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

730 mg/m³ air

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:

April 17-June 19,1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study was performed according to following guidelines: OECD 402, EU Method B.3 and in compliance with GLP Regulations (German and OECD). No significant deviations can be observed from the study guidelines, which could have an impact on the performed study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

stability not reported

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

GLP compliance:

yes (incl. QA statement)

Remarks:

German Principles of GLP (1994), OECD, GLP regulations (1983)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Gartenstraße 27, 33176 Borchen
- Age at study initiation: adult
- Weight at study initiation: 200-300g
- Fasting period before study: no data
- Housing: in Makrolon type Ill cages, each cage containing one rat
- Diet (e.g. ad libitum): Ssniff R 10 diet in pelletform (laboratory standard rat diet), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: min.5d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12h light, 12h dark

IN-LIFE DATES: From: 18-04-1996 To: 02-05-1996 (males), From: 05-06-1996 To : 16-05-1996 (females)

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorso-lumbar region (clipped free of fur)
- % coverage: app. 10%
- Type of wrap if used: no


REMOVAL OF TEST SUBSTANCE
- Washing (if done): with cleaned corn oil and absorbent paper
- Time after start of exposure: 24h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: yes

Duration of exposure:

24h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

10 (5 males and 5 females)

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation: at least twice daily; weighing: day 0 , 7 , 14
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight, dermal response, macroscopic examination

Statistics:

not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: no mortality observed

Mortality:

-no deaths following a single dermal application of Ethylene Carbonate at 2000 mg/kg bw

Clinical signs:

other: - no signs of systemic reaction to treatment

Gross pathology:

-no macroscopic abnormalities were observed for animals killed on day 14

Other findings:

-no local dermal irritations at the treatment site were observed following removal of the dressings until the end of the observation period

Interpretation of results:

GHS criteria not met

Conclusions:

The acute lethal dermal dose to rats of Ethylene carbonate was found to be greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Acute toxicity: oral (via gavage)

The Klimisch 2 study of Smyth (1954), performed according to OECD guideline 401, reported the lowest LD50 value of 10400 mg/kg bw (95% C.I. 7940 - 13620 mg/kg bw) in male Carworth-Wistar rats. Therefore, this study is designated as key study. The other reliable studies reported following LD50 values in rats: 11700 mg/kg bw (BASF, 1960), > 5000 mg/kg bw (limit test of Huntsman, 1990) and > 2000 mg/kg bw (limit test of Huels, 1996).

Acute toxicity: inhalation

The study of BASF (1960), performed according to OECD guideline 403, was selected as key study and reported a LC0 value of 730 mg/m3 air. Male and female rats were exposed for 8 hours to saturated vapour. Smith (1954) didn't observe deaths either in male albino rats that were exposed for 8 hours to saturated vapour.

Acute toxicity: dermal

The Klimisch 1 study of Krueger (1996), performed according to OECD guideline 402, was selected as key study and reported an LD0 > 2000 mg/kg bw in male and female Wistar rats. Smith (1954) reported a LD50 value > 26420 mg/kg bw in male New Zealand White rabbits.

Justification for classification or non-classification

- Acute toxicity - oral: LD50 = 10400 mg/kg bw and the substance is practically non-toxic (no further data on mortality); as the LD50 is > 2000 mg/kg bw, no classification is warranted under CLP. In addition, the LD50 of 5000 mg/kg after intraperitoneal injection does not warrant classification under CLP.

The available data on ethylene carbonate do not highlight any acute oral toxicity by the oral route of exposure. However, based on the information reported in section 7.1 about toxicokinetics of the test item, it is suggested that it was rapidly and extensively metabolized to ethylene glycol (CAS 107-21-1), with a half-life of 0.25h. Ethylene glycol is classified as R22 according to Annex I of Directive 67/548/EEC and for acute toxicity category 4 (H302) according to the Annex VI of EC 1272/2008, due to human exposure data (see also section 5.10.2 of the CSR). Given these findings, ethylene carbonate should also be classified for acute toxicity category 4.

- Acute toxicity - dermal: LD50 > 2000 mg/kg bw, no mortality and no signs of systemic reaction to treatment were observed; therefore no classification warranted under CLP

- Acute toxicity - inhalation: LC50 is > 730 mg/m³ air (limit test); the concentration tested does not enable us to decide on the classification for acute inhalation toxicity as the guideline specifies a concentration of 20 mg/L for vapours and 5 mg/L for dusts and mists.