1,1,2,3,3-pentafluoro-3-(heptafluoropropoxy)prop-1-ene

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

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)

Version / remarks:

2013

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,1,2,3,3-pentafluoro-3-(heptafluoropropoxy)prop-1-ene

EC Number:

817-766-4

Cas Number:

91891-42-8

Molecular formula:

C6F12O

IUPAC Name:

1,1,2,3,3-pentafluoro-3-(heptafluoropropoxy)prop-1-ene

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:
3M Company
- Expiration date of the lot/batch:
No data
- Purity test date:
05 Feb, 2018

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
Room temperature and humidity, protected from light and stored under enert gas
- Stability under test conditions:
Stable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
: None, dosed unchanged

Test animals / tissue source

Species:

cattle

Details on test animals or tissues and environmental conditions:

SOURCE OF COLLECTED EYES
- Source: No data
- Number of animals: No data
- Characteristics of donor animals (e.g. age, sex, weight): Greater than 35 weeks of age
- Storage, temperature and transport conditions of ocular tissue (e.g. transport time, transport media and temperature, and other conditions): In a refrigerated container containing Hanks' Balanced Salt Solution (HBSS) with penicillin-streptomycin
- Time interval prior to initiating testing: Within 24 hours
- indication of any existing defects or lesions in ocular tissue samples: Only eyes without defects were used.
- Indication of any antibiotics used: penicillin-streptomycin

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): 0.75 mL

VEHICLE: None

Duration of treatment / exposure:

10 minutes

Duration of post- treatment incubation (in vitro):

3.5 hours

Number of animals or in vitro replicates:

3

Details on study design:

SELECTION AND PREPARATION OF CORNEAS : The eyes were examined after receipt from the abattoir. Any cornea with visible evidence of neovascularization, pigmentation, opacity or scratches was discarded. Corneas free of visible defects were dissected from the surrounding tissues. A 2-3 mm rim of sclera was left attached to each cornea. The excised corneas were then placed in a container of fresh HBSS. The dissected corneas were mounted in specially designed holders (MC2, formerly Electro-Design – the manufacturer of the Op-KIT opacitometer) that were separated into anterior and posterior chambers and
filled separately. Each cornea was mounted allowing the epithelium of the cornea to project into the anterior chamber. The posterior chamber was filled with MEM solution ensuring contact with the endothelium. The anterior chamber was filled with MEM solution, ensuring contact with the epithelium. Each cornea was visually inspected again to ensure there were no defects.

QUALITY CHECK OF THE ISOLATED CORNEAS : The eyes were examined after receipt from the abattoir. Any cornea with visible evidence of neovascularization, pigmentation, opacity or scratches was discarded.

NUMBER OF REPLICATES : 3

NEGATIVE CONTROL USED : Yes, MEM Solution

SOLVENT CONTROL USED: None, no vehicle used

POSITIVE CONTROL USED : Yes, ethanol

APPLICATION DOSE AND EXPOSURE TIME : 0.75 mL, 10 minutes

TREATMENT METHOD: closed chamber

POST-INCUBATION PERIOD: yes, 3.5 hours

REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: At least two
- POST-EXPOSURE INCUBATION: 2 hours at 32 C

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: All corneas were incubated at 32 (±1)°C for an additional two hours at which time the MEM solution in the anterior and posterior chambers was removed and the holders refilled with fresh MEM solution. A measurement of opacity was taken with each treated cornea compared to the blank supplied with the OP-KIT. This reading was used in the final IVIS calculations.
- Corneal permeability: The Spectronic 20-D Colorimeter Spectrophotometer (Milton/Roy, model: 333172) was calibrated prior to use on the same day of dosing. Calibration entailed first adjusting the wavelength to 490nm and the transmittance to 0.0%. The transmittance for a sample of fresh distilled water (in a cuvette, inserted into the sample compartment) was adjusted to 100.0% on the spectrophotometer. The mode was then switched to absorbance before collecting optical density study data. After 90 (±5) minutes, the fluid from the posterior chamber of each corneal holder was removed and the amount of dye that passed through the cornea (permeability) was measured as the optical density at 490nm (i.e., the OD490nm) by spectrophotometer.

SCORING SYSTEM: In Vitro Irritancy Score (IVIS)

DECISION CRITERIA:Based on the IVIS, the test article will be classified according to the prediction model described in the EURL ECVAM DB-ALM Protocol No. 1272, a modification of the prediction model suggested by Gautheron, et al. (1994).

Results and discussion

In vitro

Results

Irritation parameter:

in vitro irritation score

Run / experiment:

Mean

Value:

0.91

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of the study (mean IVIS=0.91), the test article is not irritating to the eye in the Bovine Corneal Opacity and Permeability Test (BCOP).

Executive summary:

The eye irritation potential of the test article was evaluated in the Bovine Corneal Opacity and Permeability Test (BCOP). The study was conducted according to OECD 439 in compliance with OECD GLP principles. The test article, positive (ethanol) or negative (MEM) control was applied (0.75 mL) to three bovine corneas per test substance and incubated at 32 C using the closed-chamber method for 10 minutes. Following exposure, all corneas were washed in MEM containing phenol red. A final rinse was made with MEM without phenol red. The anterior and posterior chambers of the cornea holders were then refilled with fresh MEM solution. Opacity measurement were made following the 10 -minute exposure and MEM refill. All corneas were incubated for an additional two hour period at 32 C. A measurement of opacity was taken with each treated cornea compared to the OP-KIT blank. Immediately following the 2 hour opacity measurement, the MEM solution was removed from the anterior chamber and replaced with 1.0 mL of 0.4% sodium fluorescein solution in Dulbecco's Phosphate-buffered saline (PBS). Each cornea was then returned to the 32 C incubator. After 90 minutes, the fluid from the posterior chamber of each corneal holder was removed and the amount of dye that passed through the cornea (permeability) was measured as the optical density at 490 nm by spectrophotometer. The In Vitro Irritancy Score (IVIS) for MTDID 50667 was 0.91, negative control was 0.53, and the positive control was 34.1. Based on the results of the study (mean IVIS=0.91), the test article is not irritating to the eye in the Bovine Corneal Opacity and Permeability Test (BCOP).