[No public or meaningful name is available]

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

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:

Reaction products of 2,2'-(1,3-phenylenebis(oxy))diethanol with 2-(phenoxymethyl)oxirane and 2-isocyanatoethyl methacrylate

Cas Number:

1431303-59-1

Molecular formula:

Not assigned for UVCB substance.

IUPAC Name:

Reaction products of 2,2'-(1,3-phenylenebis(oxy))diethanol with 2-(phenoxymethyl)oxirane and 2-isocyanatoethyl methacrylate

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source (i.e. manufacturer or supplier) and lot/batch number of test material: All test articles will be supplied by the Sponsor. Lot# 6252020
- Purity, including information on contaminants, isomers, etc.: No data.

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature and humidity and in a dark cabinet.
- Stability and homogeneity of the test material in the vehicle/solvent under test conditions (e.g. in the exposure medium) and during storage: No data.
- Stability in the medium, i.e. sensitivity of the test material to hydrolysis and/or photolysis: No data.
- Solubility and stability of the test material in the solvent/vehicle and the exposure medium: No data.
- Reactivity of the test material with the incubation material used (e.g. plastic ware): No data.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing (e.g. warming, grinding): The test article was used as received, warmed in an incubator at 33ºC prior to dosing.
- Preliminary purification step (if any): No.
- Final concentration of a dissolved solid, stock liquid or gel: Surfactants will be tested at a concentration of 10% weight/volume or volume/volume
(v/v) in 0.9% physiological saline (or other vehicle as specified by the Sponsor). All
other liquids are tested undiluted.

Test animals / tissue source

Species:

cattle

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Cattle. Bovine eyes (at least six months old) will be obtained from an abattoir and will be transported to the laboratory in a refrigerated container containing Hanks’ Balanced
Salt Solution (HBSS) with penicillin-streptomycin.

Test system

Vehicle:

Hank's balanced salt solution

Controls:

yes, concurrent vehicle

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.75 ml
- Concentration (if solution):Solid test articles will be prepared as a 20% solution or suspension in 0.9% physiological saline

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.75 ml.

Duration of treatment / exposure:

After 10 (±1) minutes, the test article,
ethanol, or MEM was removed from the epithelium of the cornea and anterior chamber of the holder by
washing with MEM solution containing phenol red. A final rinse was made with MEM without phenol red.
The anterior and posterior chambers of the holders were then refilled with fresh MEM solution.

Duration of post- treatment incubation (in vitro):

All corneas will be incubated at 32 (±1)°C until immediately prior to the two hour scores, at which time the MEM solution in the anterior and posterior
chambers will be removed and the holders refilled with fresh MEM solution

Number of animals or in vitro replicates:

3

Details on study design:

NUMBER OF REPLICATES : 3

NEGATIVE CONTROL USED : 3

SOLVENT CONTROL USED (if applicable) : 3

POSITIVE CONTROL USED : 3

APPLICATION DOSE AND EXPOSURE TIME : A volume of 0.75 ml of the liquid test article, MEM solution or ethanol will be applied to the epithelium in a manner that ensures the entire cornea will be covered. 10 minute exposure.

TREATMENT METHOD: closed chamber

POST-INCUBATION PERIOD: yes/no. If YES please specify duration

REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: After 10 (±1) minutes, the test article,
ethanol, or MEM was removed from the epithelium of the cornea and anterior chamber of the holder by washing with MEM solution containing phenol red. A final rinse was made with MEM without phenol red. The anterior and posterior chambers of the holders were then refilled with fresh MEM solution.

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: Yes
- Corneal permeability: passage of sodium fluorescein dye measured with the aid of [UV/VIS spectrophotometry / microtiter plate reader] (OD490)
- Others (e.g, pertinent visual observations, histopathology): (please specify)

SCORING SYSTEM: In Vitro Irritancy Score (IVIS)

DECISION CRITERIA: Criteria defined in TG 437.

Results and discussion

In vitro

Results

Results 1

Irritation parameter:

in vitro irritation score

Run / experiment:

Mean

Value:

-0.62

Vehicle controls validity:

not examined

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

fluorescein leakage

Remarks:

Corrected Mean optical density

Run / experiment:

Mean

Value:

0.003

Vehicle controls validity:

not examined

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

cornea opacity score

Run / experiment:

Mean

Value:

-0.66

Vehicle controls validity:

not examined

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Other effects / acceptance of results:

OTHER EFFECTS:
- Visible damage on test system: None.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of the study, ERGP-IEM is not considered an eye irritant.

Executive summary:

The corneal irritation and damage potential of ERGP-IEM was evaluated in the Bovine Corneal Opacity and Permeability test (BCOP). The study was performed in compliance with EPA GLP 40 CFR 160 and 792, FDA GLP 21 CFR 58, and OECD GLP (1997). The test method was based on OECD 437 (2009). A pretest was performed to measure pre-exposure opacity of the test corneas against the control corneas blanks. The corneas were prepared in cell culture and incubated at 32˚C for at least 1 hour prior to exposure. For the BCOP exposure, corneas (3/test article) were treated with 0.75 mL of undiluted liquid expressed from the test article and then were incubated at 32˚C for 10 minutes. At the end of the exposure, the corneas were washed and incubated in fresh medium for an additional 2 hours. Opacity was evaluated using an opacitometer after the 2 hour post-exposure incubation. Following opacity readings, the cell culture medium was replaced with Na-fluorescein medium and incubated for approximately 90 minutes. Following the 90 minute exposure, permeability was measured. The mean in vitro irritation score (IVIS) was calculated and the scores were classified according to protocol defined categories. Ocular exposure to ERGP-IEM in the test resulted in an IVIS = -0.62, the mean opacity was -0.66 and the mean permeability score was 0.003. Based on the results of the study, ERGP-IEM is not considered an eye irritant.