2-[methyl[(nonafluorobutyl)sulphonyl]amino]ethyl methacrylate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)

Deviations:

no

Remarks:

No deviations occurred that impacted the quality of the study or interpretability of the results.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

C4 sulfonamido methacrylate

IUPAC Name:

C4 sulfonamido methacrylate

Details on test material:

- Name of test material (as cited in study report): 2-Propenoic acid, 2-Methyl-, 2-[Methyl[(Nonafluorobutyl)Sulfonyl]Amino]Ethyl ester, FZ-9262
- Physical state: white to grey waxy solid
- Analytical purity: 99.5%
- Storage condition of test material: at room temperature in the dark

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 3M Company, Lot 40010
- Expiration date of the lot/batch: No data
- Purity test date: 25 May, 2017

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature.
- Stability under test conditions: No data
- Solubility and stability of the test substance in the solvent/vehicle: Soluble

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: 1.00 g of test article was brought to a total volume of 5 ml with 0.9% saline and mixed, to yield a 20% concentration.

Test animals / tissue source

Species:

cattle

Details on test animals or tissues and environmental conditions:

SOURCE OF COLLECTED EYES
- Source: Spear Products
- Number of animals: No data
- Characteristics of donor animals (e.g. age, sex, weight): Animals were at least 6 months old.
- Storage, temperature and transport conditions of ocular tissue (e.g. transport time, transport media and temperature, and other conditions): Eyes were transported in Hanks' Balanced Salt solution and penicillin-streptomycin in a refrigerated container.
- Time interval prior to initiating testing: No data
- indication of any existing defects or lesions in ocular tissue samples: Any eye with a cornea exhibiting evidence of vascularization, pigmentation, opacity or scratches was discarded.
- Indication of any antibiotics used: Penicillin-streptomycin

Test system

Vehicle:

physiological saline

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): 20% (200 mg/mL)

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.9% sodium chloride irrigation (saline).
- Concentration (if solution): 0.9%
- Lot/batch no. (if required): Lot J6P916
- Purity: No data

Duration of treatment / exposure:

4 hours

Duration of post- treatment incubation (in vitro):

None

Number of animals or in vitro replicates:

3 corneas per treatment and control solution.

Details on study design:

SELECTION AND PREPARATION OF CORNEAS: Any eye with a cornea exhibiting evidence of vascularization, pigmentation, opacity or scratches was discarded.

QUALITY CHECK OF THE ISOLATED CORNEAS: Yes, any eye with a cornea exhibiting evidence of vascularization, pigmentation, opacity or scratches was discarded.

NUMBER OF REPLICATES: 3 per treatment

NEGATIVE CONTROL USED: MEM

SOLVENT CONTROL USED (if applicable): 0.9% saline

POSITIVE CONTROL USED: Imidazole in 0.9% saline

APPLICATION DOSE AND EXPOSURE TIME: 0.75 mL of the test article solution, 4 hour exposure.

TREATMENT METHOD: Test article exposure: open-chamber. Controls: closed-chamber.

POST-INCUBATION PERIOD: No

REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: 2
- POST-EXPOSURE INCUBATION: None

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: Determined using an OP-KIT opacitometer produced by Electro-Design Corporation of Riom, France.
- Corneal permeability: passage of sodium fluorescein dye measured with the aid of UV spectrophotometry (OD490)

SCORING SYSTEM: In Vitro Irritancy Score (IVIS)

DECISION CRITERIA: Based on the IVIS score, the test article was classified according to the prediction model described in DBALM Protocol No. 1271, a modification of the prediction model suggested by Gautheron, et al., (1994).
IVIS:
0 to 3: Non-irritatant
3.1 to 25: Mild Eye Irritant
25.1 to 55: Moderate Eye Irritant
55.1 and above: Severe/Corrosive Eye Irritant

Results and discussion

In vitro

Results

Irritation parameter:

in vitro irritation score

Run / experiment:

Mean

Value:

ca. -2.97

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Remarks:

A negative IVIS score was derived (-2.97)

In vivo

Irritant / corrosive response data:

The mean IVIS for test article-treated corneas was -2.97. The corrected mean opacity score was -3.00 and the corrected mean optical density was 0.002.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of the study, the test article is not irritating to the eye.

Executive summary:

The ocular irritation potential of the test article was evaluated in the Bovine Corneal Opacity and Permeability Test (BCOP). The study was conducted according to OECD 437 and was conducted in compliance with OECD GLP regulations. The test article (off-white powder) was dissolved in 0.9% saline to yield a 20% concentration (200 mg/mL). A volume of 0.75 ml of the 20% (w/v) test article formulation in saline, 20% (w/v) imidazole formulation in saline, MEM solution or 0.9% saline was applied to the epithelium of each of the three test article corneas, three positive control corneas, three negative control corneas and three vehicle control corneas in a manner which ensured that the entire cornea was covered. The test article corneas were dosed via the open-chamber method. The negative, positive, and vehicle controls were dosed via the closed-chamber method. All holders and corneas were placed in a horizontal position (anterior side up) in the 32 C incubator for four hours. Following the exposure, all tissues were washed 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. Opacity measurements were made following the four-hour exposure and MEM solution refill. Immediately following the four-hour opacity measurement, the MEM solution was removed from the anterior chamber and replaced with 1.0 mL of 0.5^ sodium fluorescein solution in Dulbecco's phosphate-buffered saline (PBS). Each holder was then returned to the 32 C incubator in a horizontal position (anterior side up) ensuring contact with the fluorescein and the cornea. After 90 minutes, the fluid from the posterior chamber was removed and the amount of dye that passed through the cornea (permeability) was measured as the optical density at 490 nm by a spectrophotometer. Negative, vehicle and positive controls performed as expected, indicating a valid test system. A 4 hour exposure to the test article resulted in a mean In Vitro Irritancy Score (IVIS) of -2.97, corrected mean opacity score of -3.00 and corrected mean optical density of 0.002. Based on the results of the study, the test article is not irritating to the eye.