Ethylene carbonate

Endpoint summary

Description of key information

Ethylene carbonate was observed to be not irritating to rabbit skin (Blanchard, 2001) and moderately irritating to rabbit eyes (Johnson, 2001).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 15-19,2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study was performed according to following guidelines: OECD 404, EU Method B.4, EPA OPPTS 870.2500 and in compliance with to the GLP Regulations. 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 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

stability not reported

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Principles of method if other than guideline:

26% humidity was recorded: this is slightly outside the range specified in the study protocol. This deviation was not considered to have affected the integrity or validity of the study.

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England.
- Age at study initiation: at least 11 weeks old (adult)
- Weight at study initiation: 2.3-2.4 kg
- Housing: individually in stainless steel cages with perforated floors in Building R17 Room 10.
- Diet (e.g. ad libitum): a standard laboratory rabbit diet (Special Diet Services STANRAB (P) SQC pellet), ad libitum
- Water (e.g. ad libitum): potable water ( Anglian) for human consumption, ad libitum.
- Acclimation period: min.5d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-20.5°C
- Humidity (%): 26-36 %
- Photoperiod (hrs dark / hrs light): 12h dark/12h light


IN-LIFE DATES: From: 15 Feb 2000 To: 19 Feb 2000

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: OECD 404: untreated area of the test animal serves as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml

Duration of treatment / exposure:

-3min, 1h, 4h

Observation period:

4d

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: app.25 mm x 25 mm, dorso-Iumbar region (clipped free of fur) /
- Type of wrap if used: 2-ply 25mm x 25 mm porous gauze pad, each treatment site was covered with "Elastoplast" elastic adhesive dressing.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with warm water (36 to 37°C)
- Time after start of exposure: 3 min, 1 and 4h


SCORING SYSTEM: observation
Draize Evaluation of Dermal Irritation

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: 3 min, 1 and 4 h exposure (intact skin), no dermal irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: 3 min, 1 and 4 h exposure (intact skin), no dermal irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: 3 min, 1 and 4 h exposure (intact skin), no dermal irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: 3min, 1 and 4 hours exposure (intact skin), no dermal irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: 3 min, 1 and 4 h exposure (intact skin), no dermal irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: 3 min, 1 and 4 h exposure (intact skin), no dermal irritation

Irritant / corrosive response data:

There were no signs of toxicity or ill health in any rabbit during the observation period. (on day 1, 2, 3 or 4)

Interpretation of results:

GHS criteria not met

Conclusions:

A single semi-occlusive application of JEFFSOL Ethylene Carbonate (ultra pure grade) to intact rabbit skin for four hours elicited no dermal irritation.
JEFFSOL Ethylene Carbonate (ultra pure grade) will not require labelling with the risk phrase R38, "Irritating to skin", in accordance with Commission Directive 93/21IEEC.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November 14 -December 15, 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study was performed according to following guidelines: OECD 405, EU Method B.5, EPA OPPTS 870.2400 and in compliance with the GLP Regulations. No significant deviations can be observed from the study guidelines, which could have an impact on the performance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

stability not reported

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Limited, Margate, Kent, UK.
- Age at study initiation: young adults
- Weight at study initiation: 2.969-3.914 kg
- Housing: individually, in cages suitable for animals of this strain and the weight range expected during the course of the study.
- Diet (e.g. ad libitum): Diet (STANRAB SQC), supplied by Special Diet Services Limited, Witham, Essex, UK, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: min.5d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18°C±3°C
- Humidity (%): 30-70
- Air changes (per hr): a minimum of 15 changes/hour,
- Photoperiod (hrs dark / hrs light): 12h dark/12h light


IN-LIFE DATES: From: 20 Nov 2000 To: 15 Dec 2000

Vehicle:

unchanged (no vehicle)

Controls:

other: OECD 405: untreated eye of the test animal serves as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

Duration of treatment / exposure:

1-2 seconds

Observation period (in vivo):

10 days

Number of animals or in vitro replicates:

3 (1 male and 2 females)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with water
- Time after start of exposure: 1 day


SCORING SYSTEM: observation
Draize and a modified form of the Kay and Calendra scoring system


TOOL USED TO ASSESS SCORE: fluorescein staining

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal 98

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal 106

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal 107

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal 98

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal 106

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal 107

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal 98

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal 106

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal 107

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within: 10 days

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

Animal 98

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal 106

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal 107

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritant / corrosive response data:

Additional signs of irritation consisted of oedematous, erythematous or convoluted eyelids; lachrymatory or Harderian discharge; haemorrhage of
the nictitating membrane; dried secretion around the periorbital skin and eyelids closed due to discharge.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

JEFFSOL Ethylene Carbonate is a moderate irritant (class 5 on a 1-8 scale) to the rabbit eye. According to the criteria specified in the CLP Regulation (EC) No 1272/2008, JEFFSOL Ethylene Carbonate should be classified as an eye irritant substance category 2 (reversible eye effects).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / corrosion:

Two Klimisch 1 studies were identified for the skin irritation / corrosion endpoint (Blanchard, 2001 and Johnson, 2001), which were performed according to OECD guideline 404, EU method B4 and EPA OPPTS 870.2500 method. The study of Blanchard (2001) was selected as key study based on the fact that the most pure grade of the substance was tested. A single semi-occlusive application of JEFFSOL Ethylene Carbonate (ultra pure grade) to intact rabbit skin for four hours elicited no dermal irritation. In addition, BASF (1960) reported that this substance has no skin irritant properties. Gad (1986) reported negligible irritation to the skin in rabbits. In contrary, Johnson (2001) reported that this substance is a slight irritant following a single four hour application to rabbit skin. Similar findings were reported by Smyth (1954) and Huels (1984). However, according to the criteria specified in the CLP Regulation (EC) No 1272/2008, ethylene carbonate should not be classified as a skin irritant substance.

Eye irritation / corrosion:

Two Klimisch 1 studies were available. The study from Johnson (2001), performed according to OECD guideline 405, EU method B5 and EPA OPPTS 870.2400 method, was chosen as the key study. In this study, the observed irritating effects were fully reversible within 4 days (cornea), 2 days (iris) and 10 days (conjunctivae). Also Huntingdon (2001) found irritant effects, which were fully reversible within 7 days (on cornea and iris) and within 14 days (on conjunctivae for redness and chemosis).

The older study from Huels (1960) is scientifically interesting, but not definitive. The substance is described to be colorless needles, which doesn’t fit the description in other studies (white solid). Moreover, the observed effects are mechanical effects. The BASF study (1960) observed the effects only during 7 days. The cornea effect might have disappeared at longer observation period. The K1 studies have clearly a longer observation period. The study from Gad et al. (1986) was a screening study only, performed on a substance with unknown purity. The results were not detailed: a comparison with the Draize score and the Green’Scale are presented only.

Based on the more recent studies (both considered to be highly reliable), the substance is evaluated to be moderately irritating.

Justification for classification or non-classification

- Based on the available data and according to the criteria of the CLP Regulation No 1272/2008 ethylene carbonate should not be classified as a skin irritant substance.

- Based on the available data and according to the criteria of the CLP Regulation No 1272/2008 ethylene carbonate should be classified as a category 2 eye irritant substance (causes serious eye irritation).