[2-[(2-methyl-1-oxoallyl)oxy]ethyl] hydrogen succinate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

[2-[(2-methyl-1-oxoallyl)oxy]ethyl] hydrogen succinate

EC Number:

244-096-4

EC Name:

[2-[(2-methyl-1-oxoallyl)oxy]ethyl] hydrogen succinate

Cas Number:

20882-04-6

Molecular formula:

C10H14O6

IUPAC Name:

4-{2-[(2-methylprop-2-enoyl)oxy]ethoxy}-4-oxobutanoic acid

impurity 1

Reference substance name:

2-hydroxyethyl methacrylate

EC Number:

212-782-2

EC Name:

2-hydroxyethyl methacrylate

Cas Number:

868-77-9

Molecular formula:

C6H10O3

IUPAC Name:

2-hydroxyethyl methacrylate

impurity 2

Reference substance name:

Succinic acid

EC Number:

203-740-4

EC Name:

Succinic acid

Cas Number:

110-15-6

Molecular formula:

C4H6O4

IUPAC Name:

succinic acid

Test material form:

liquid

Details on test material:

- Name as cited in the report: Methacryloyloxyethyl succinate
- EC-name: [2-[(2-methyl-1-oxoallyl)oxy]ethyl] hydrogen succinate
- CAS: 20882-04-6
- EC-No.: 244-096-4
- Batch No.: 3903/64
- Storage: 4-8°C, protected from heat and sunlight
- Description: yellowish liquid
- Density: 1.1884 g/kg
- Molecular weight: approx. 230 g/mol
- Formula: C10H14O6
- Purity: 84% (NMR)

Test animals / tissue source

Species:

other: Bovine Corneas

Strain:

other: not applicable

Details on test animals or tissues and environmental conditions:

The assay uses isolated corneas obtained as a by-product fram animals freshly slaughtered at the abattoir A. Moksel AG, Buchloe, Germany.
On the test day, fresh eyes were collected from the slaughterhouse and were transported in HBSS containing Pen/Strep on ice to the laboratories.
Immediately after arrival of the eyes, cornea preparation was initiated.
The eyes were carefully examined for defects and any defective eyes were discarded.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: 3 corneas each for negative or positive control

Amount / concentration applied:

750 µL

Duration of treatment / exposure:

10 min

Duration of post- treatment incubation (in vitro):

2 h (illuminance)
3.5 h (optical density)

Number of animals or in vitro replicates:

3 corneas

Details on study design:

- 3 corneas for the test item
- 3 corneas as negative controls treated with physiological saline 0.9% NaCl
- 3 corneas as positive control treated with ethanol 100%
- The BCOP assay is considered to be valid if the in vitro irritation score obtained with the positive control falls within the two standard deviations of the current historical mean.

Results and discussion

In vitro

Results

Results 1

Irritation parameter:

in vitro irritation score

Run / experiment:

Mean

Value:

138.17

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Results 2

Irritation parameter:

cornea opacity score

Run / experiment:

Mean

Value:

127.61

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

RESULTS

Cornea No.	Test Item	Corr. Opacity	Corr. OD490	IVIS
1	Neg. Control	2.53	0.007
2	Neg. Control	0.57	0.005
3	Neg. Control	0.38	0.006
mean	Neg. Control	1.16	0.006	1.25
4	Pos. Control	26.69	1.302
5	Pos. Control	34.61	1.119
6	Pos. Control	23.15	1.079
mean	Pos. Control	28.15	1.167	45.65
7	Test Item	128.22	0.648
8	Test Item	136.57	0.592
9	Test Item	118.04	0.873
mean	Test Item	127.61	0.704	138.17

The eye irritancy potential of Methacryloyloxyethyl succinate was investigated in the bovine corneal opacity and permeability assay.

- Preparation of the test item: tested as provided by the sponsor

- Mean in vitro irritation score: 138.17

- Classification: UN GHS Category 1

The in vitro irritation score obtained with the positive control fell within the two standard deviations of the current historical mean and therefore this assay is considered to be valid.

HISTOPATHOLOGY

Test Item treated corneas revealed a minor increase of vacuolated epithelium and in apoptotic bodies, as well as in one case a minor degree of focally flattened epithelium.

The appearance of single cell nuclei with apoptosis was also recorded in negative and positive controls.

In all positive control samples, there was vacuolation of the basal epithelium (swelling).

No unusual findings were recorded in negative controls.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Remarks:

Criteria used for interpretation of results: other: BCOP standard evaluation criteria

Conclusions:

According to the evaluation criteria the test item Methacryloyloxyethyl succinate is classified into UN GHS Category 1.

Under the conditions of this study, Methacryloyloxyethyl succinate caused a minor increase in vacuolated epithelium and in apoptotic bodies, and in one case a minor degree of focally flattened epithelium.

Executive summary:

The eye irritancy potential of Methacryloyloxyethyl succinate was investigated in the bovine corneal opacity and permeability assay.

- Preparation of the test item: tested as provided by the sponsor

- Mean in vitro irritation score: 138.17

- Classification: UN GHS Category 1

The in vitro irritation score obtained with the positive control fell within the two standard deviations of the current historical mean and therefore this assay is considered to be valid.