2,3,3,4,4-pentafluoro-5-methoxy-2,5-bis[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]tetrahydrofuran

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016

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 i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)

Version / remarks:

2013

Deviations:

yes

Remarks:

The incubation time after the test item removal was 16 minutes too short. Since the positive and negative control met the acceptance criteria, this does not affect the study results.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,3,3,4,4-pentafluoro-2,5-bis(1,1,1,2,3,3,3-heptafluoropropan-2-yl)-5-methoxyoxolane

EC Number:

812-244-2

Cas Number:

957209-18-6

Molecular formula:

C11H3F19O2

IUPAC Name:

2,3,3,4,4-pentafluoro-2,5-bis(1,1,1,2,3,3,3-heptafluoropropan-2-yl)-5-methoxyoxolane

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Lot # 20003, unit 0022
- Expiration date of the lot/batch: 30 March, 2018
- Purity test date: 30 March, 2016

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: None

FORM AS APPLIED IN THE TEST: Undilluted

Test animals / tissue source

Species:

cattle

Strain:

other: Not specified.

Details on test animals or tissues and environmental conditions:

SOURCE OF COLLECTED EYES
- Source: Vitelco's, Hertogenbosch, The Netherlands
- Number of animals: Not specified
- Characteristics of donor animals: Young
- Storage, temperature and transport conditions of ocular tissue: Eyes were collected and transported in physiological saline suitable container under cooled conditions as soon as possible after slaughter.
- Time interval prior to initiating testing: Not specified.
- indication of any existing defects or lesions in ocular tissue samples: Eyes were checked for unacceptable defects such as opacity, scratches, pigmentation and neovascularization. Those exhibiting defects were discarded.
- Indication of any antibiotics used: Not specified.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 750 uL

Duration of treatment / exposure:

10 minutes

Duration of post- treatment incubation (in vitro):

120 minutes

Number of animals or in vitro replicates:

3

Details on study design:

SELECTION AND PREPARATION OF CORNEAS: Eyes were checked for unacceptable defects such as opacity, scratches, pigmentation and neovascularization. Those exhibiting defects were discarded. The isolated corneas were stored in a petri dish with cMEM containing 1% (v/v) L-glutamine and 1% (v/v) Fetal Bovine Serum. The isolated corneas were mounted in a corneal holder of BASF with the endothelial side against the O-ring of the posterior half of the holder. The anterior half of the holder was positioned on top of the cornea and tightened with screws. The compartments of the corneal holder were filled with cMEM. The corneas were incubated for a minimum of 1 hour at 32 C.

QUALITY CHECK OF THE ISOLATED CORNEAS: After the incubation period, the medium was removed from both compartments and replaced with fresh cMEM. Opacity determinations were performed on each of the corneas using an opacitometer. The opacity of each cornea was read against a cMEM filled chamber, and the initial opacity reading was recorded. Corneas that had an inital opacity reading higher than 7 were not used. Three corneas were selected at random for each treatment group.

NUMBER OF REPLICATES: 3

NEGATIVE CONTROL USED: Physiological saline

POSITIVE CONTROL USED: Ethanol

APPLICATION DOSE AND EXPOSURE TIME: 750 uL for 10 minutes.

TREATMENT METHOD: closed chamber

POST-INCUBATION PERIOD: No

REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: 2

- POST-EXPOSURE INCUBATION: 120 minutes

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: Measured by diminution of light passing through the cornea.
- Corneal permeability: passage of sodium fluorescein dye measured with the aid of microtiter plate reader (OD490)

SCORING SYSTEM: In Vitro Irritancy Score (IVIS)

DECISION CRITERIA: please specify if the decision criteria as indicated in the TG was used: Yes, decisions criteria as indicated in the TG were utilized.

Results and discussion

In vitro

Results

Irritation parameter:

in vitro irritation score

Run / experiment:

Mean

Value:

ca. -0.4

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Yes
- Acceptance criteria met for positive control: Yes

In vivo

Other effects:

The corneas treated with the test article showed opacity values ranging from -0.5 to -0.1 and permeability values ranging from -0.001 to 0.007. The corneas were clear after the 10 minutes of treatment with the test article. No pH effects of the test article were observe on the rinsing medium. The in vitro irritancy scores ranged from -0.5 to 0.0 after 10 minutes of treatment with the test article.

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 an ocular irritant.

Executive summary:

The ocular irritation potential of the test article was evaluated in the Bovine Corneal Opacity and Permeability test (BCOP test). The study was conducted according to OECD 437 (2013) in compliance with OECD GLP (1997). The test article was applied unchanged (750 uL) directly on top of the corneas (n=3). Negative controls (physiological saline) and positive controls (ethanol) were tested concurrently. The controls were within historical laboratory ranges indicating that the test conditions were adequate and that the test system functioned properly. The test article did not induce ocular irritation through either endpoint, resulting in a mean in vitro irritancy score of -0.4 after 10 minutes of exposure. Based on the results of the study, the test article is not an ocular irritant.