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Description of key information

In a weight-of-evidence approach, available studies from other ionic liquids sharing either the kationic or the anionic part with EMIM acetate were used to assess its skin potential.

One analogue salt is different from the target substance by the length of one alkyl side chain of the cation (ethyl versus methyl). The other analogue shares the cation, but has a different anion (sulfate versus acetate).

The worst case classification is used for the target substance: Skin irritant (GHS Cat 2).

For eye irritation an identical weight-of-evidence approach as well as a GLP-Study for the original substance EMIM-Acetate were used to assess the eye irritation potential.

Here the worst case classification is non irritating to eyes (no GHS classification).

On the basis of the available data for eye irritation the classification of the skin irritation potential is plausible.

For the analogue substances, the following experimental data are available:

Skin:

Skin irritant Category 2, no skin corrosion potential, in vitro EpiDerm/SCT (OECD 431, Klimish 2), CAS: 1040916-84-4 (1,3-diethyl-1H-imidazol-3-ium acetate)

No skin irritation potential, in vivo acute dermal irritation assay (OECD 404, Klimish 1), CAS: 516474-01-4 (1-Ethyl-3-methylimidazolium methyl sulfate)

Eye:

No eye irritation potential, in vivo acute eye irritation in rabbit (OECD 405, Klimish 1), CAS: 516474-01-4

No potential to cause serious eye damage, ex vivo assay for identifying serious eye damage potential BCOP (OECD 437, Klimish 1), CAS: 1040916-84-4

No eye irritation potential, in vitro EpiOcular (no guideline, Klimish 2), CAS: 1040916-84-4

No eye irritation potential, in vitro EpiOcular (OECD 492), CAS 143314 -17 -4

These findings are in accordance with local irritant effects observed in the acute dermal toxicity study (BASF, 2010).

Local effects such as erythema, edema and parital severe incrustations and scaling were found in all groups but reversed within observation time.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Data on the test material itself were not available.

In a weight-of-evidence approach, available studies for the structural cation analogue 1-Ethyl-3-methylimidazolium methyl sulfate (CAS: 516474-01-4) and the structural analog anion 1,3-diethyl-1H-imidazol-3-ium acetate (CAS: 1040916-84-4) are used to assess the irritation and corrosion potential of the test material.

skin:

in vivo, OECD 404:

The potential of 1-Ethyl-3-methylimidazolium Methylsulfat to cause acute dermal irritation or corrosion was assessed by a single topical application of an amount of 0.5 mL of the test item for 4 hours to the intact skin of three White New Zealand rabbits (stepwise procedure starting with one animal and supplementing two additional animals), using a patch of 2.5 cm x 2.5 cm, covered with semi occlusive dressing.

After removal of the patch the application area was washed off.

The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch.

Very slight erythema was observed in one animal up to 24 hours after removal of the patch.

This cutaneous reaction was reversible in this animal within 48 hours after removal of the patch.

Mean scores over 24,48 and 72 hours for each animal were 0.3, 0.0 and 0.0 for erythema and 0.0, 0.0 and 0.0 for edema.

Considering the described cutaneous reactions as well as the average score for irritation, 1-Ethyl-3-methylimidazolium Methylsulfat does not show a skin irritating potential under the test conditions chosen.

in vitro, OECD 431:

The objective of the test was to assess the potential for corrosive activity of the test material upon first contact with skin. The assessment of the skin corrosion/irritation potential is included in international regulatory requirements for the testing of chemicals. Due to animal welfare reasons corrosivity was determined using the reconstructed human epidermal model EpiDerm.

The mean viability of two tissues per exposure time was measured after incubation of the undiluted liquid test material.

The viability was 105 % and 107% compared to the negative control after the exposure time of 3 min and 1 hour, respectively.

Valid positive control with mean viability of 26 % after 3 min exposure and 7 % after 1 hour exposure, compared to negative control.  

Based on the observed results it was concluded, that the test material does not show a corrosive potential in the EpiDerm skin corrosion test under the test conditions chosen. The result does not exclude an irritation potential of the test substance.

In a conservative approach, the test material might be assumed to be irritant but for a final assignment of a risk phrase at present, results from another study would be needed.

Eye:

ex vivo, OECD 437:

The potential of the test item to cause serious damage to the eyes was assessed by a single topical application of 750 μL of the undiluted test substance to the epithelial surface of isolated bovine corneas.

Three corneas were treated with the test substance for 10 minutes followed by a 2-hours post-incubation period.

Corneal opacity was measured quantitatively as the amount of light transmission through the cornea. Permeability was measured quantitatively as the amount of sodium fluorescein dye that passes across the full thickness of the cornea. Both measurements were used to calculate an In Vitro Irritancy Score of the test substance relative to the control corneas.

Based on the observed results and applying the evaluation criteria it was concluded, that the test item does not cause serious eye damage in the Bovine Corneal Opacity and Permeability Test (BCOP Test) under the test conditions chosen.

The test method according to the regulatory accepted protocol at the time of reporting doesnot allow for the evaluation of eye irritation. The result does not exclude an irritation potential of the test substance. For final assignment of a risk phrase at present, results from another study would be needed.

in vitro, EpiOcular:

The potential of the test item to cause ocular irritation was assessed by a single topical application of 50 μL of the undiluted test substance to a reconstructed three dimensional human cornea model (EpiOcular™).

Two EpiOcular™ tissue samples were incubated with the test substance for 30 minutes followed by a 2-hours post-incubation period.

Tissue destruction was determined by measuring the metabolic activity of the tissue after exposure/post-incubation using a colorimetric test. The reduction of mitochondrial dehydrogenase activity, measured by reduced formazan production after incubation with a tetrazolium salt (MTT) was chosen as endpoint. The formazan production of the test substance treated epidermal tissues is compared to that of negative control tissues. The quotient of the values indicates the relative tissue viability.

The EpiOcular™ eye irritation test showed the following results:

The test substance is not able to reduce MTT directly.

The mean viability of the test-substance treated tissues was 71%.

Based on the observed results and applying the evaluation criteria it was concluded, that the test item does not show an eye irritation potential in the EpiOcular™ eye irritation test under the test conditions chosen.

in vivo, OECD 405:

The potential of 1-Ethyl-3-methylimidazolium Methylsulfat to cause damage to the conjunctiva, iris or cornea was assessed by a single ocular application of 0.1 mL of the test item to one eye of three White New Zealand rabbits (stepwise procedure starting with one animal and supplementing two additional animals). About 24 hours after application the eye was rinsed with tap water.

The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application and then in weekly intervals until day 14.

Conjunctival redness (grade 1 and 2), conjunctival Chemosis (grade 1 and 2) and discharge (grade 1 to 3) were observed in the animals up to 72 hours after the administration.

No corneal and iris lesions were noted in any animal at any examination timepoint.

Additional findings like contracted pupil and injected scleral vessels (in a circumscribed area or circular) were noted in the animals during the observation period.

These ocular reactions were reversible in all animals within 14 days after application at the latest.

Mean scores calculated for each animal over 24,48 and 72 hours were 0.0, 0.0 and 0.0 for corneal opacity, 0.0, 0.0 and 0.0 for iris lesions, 1.3, 1.0 and 1.0 for redness of the conjunctiva and 0.3, 1.0 and 0.0 for chemosis.

Considering the described ocular reactions as well as the average score for irritation, 1-Ethyl-3-methylimidazolium Methylsulfat does not show an eye irritation potential under the test conditions chosen.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008.

As a result the substance is to be classified for skin irritation Category 2 but not classified for eye irritation under Regulation (EC) No. 1272/2008.