1-({[(2,5-dioxopyrrolidin-1-yl)oxy]carbonyl}oxy)ethyl 2-methylpropanoate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Reconstitured Human Cornea: Determination of eye irritation potential using the SkinEthic Reconstituted Human Corneal model (RHC, SkinEthic Labs, Nice, France) following treatment periods of 10 and 60 minutes. The test is based on the hypothesis that irritant materials are able to penetrate the corneal epitelial tissue and are sufficiently cytotoxic to cuase cell death.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

1-({[(2,5-dioxopyrrolidin-1-yl)oxy]carbonyl}oxy)ethyl 2-methylpropanoate

EC Number:

700-402-2

Cas Number:

860035-10-5

Molecular formula:

C11H15NO7

IUPAC Name:

1-({[(2,5-dioxopyrrolidin-1-yl)oxy]carbonyl}oxy)ethyl 2-methylpropanoate

Test animals / tissue source

Species:

human

Test system

Vehicle:

unchanged (no vehicle)

Results and discussion

In vitro

Results

Results 1

Irritation parameter:

other: relative mean viability

Run / experiment:

10 mins

Value:

ca. 36.8

Negative controls validity:

valid

Remarks on result:

positive indication of irritation

Results 2

Irritation parameter:

other: relative mean viability

Run / experiment:

60 mins

Value:

ca. 4.4

Negative controls validity:

valid

Remarks on result:

positive indication of irritation

Other effects / acceptance of results:

RHC Model: The relative mean viability of the test material treated tissue was 36.8% after 10minutes and 4.4% after 60 minute exposure.

Any other information on results incl. tables

results are from in vitro/ ex vivo studies and time points, score and max score are not applicable endpoints

Applicant's summary and conclusion

Interpretation of results:

moderately irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

GSK1873183A was considered to be irritating to eyes based upon the results of the in vitro/ex vivo studies.

Executive summary:

An in vitro test strategy was adopted to assess the potential eye irritation of GSK1873183A. In the rabbit enulceated eye test (REET), 0.1ml of test material was applied to the cornea of each of three enucleated eyes which had been maintained ata temperature of 32deg C within the superfusion chamber. A further two enucleated eyes were treated with saline solution as controls. Assessment or corneal cloudiness was made approx 60, 120, 180 and 240mins following treatment. Examination of the eye facilitated by use of a slit-lamp biomicroscope and the thickness of the cornea was measured using an ultrasonic pachymeter. In the Human Reconsititued Corneal Model (RHC) determination of eye irritation potential was assessed using the SkinEthic Reconstituted Human Corneal model (RHC, SkinEthic Labs, Nice, France) following treatment periods of 10 and 60 minutes. The test is based on the hypothesis that irritant materials are able to penetrate the corneal epitelial tissue and are sufficiently cytotoxic to cuase cell death.

The REET assay indicated that GSK1873183A is unlikely to have potential to cause severe ocular irritancy in vivo. The RHC model indicated thatthe test material is likley to be a moderate eye irritant and should be classified as R36; Irritating to eyes (GHS Category 2A)