Reaction mass of bis(polysubstituted hexanoic acid) bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl) diphosphate and bis(polysubstituted hexanoic acid) 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl phosphate and polysubstituted hexanoic acid bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl) hydrogen diphosphate and polysubstituted hexanoic acid bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl) phosphate and polysubstituted hexanoic acid 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl hydrogen phosphate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

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:

Conducted according to guideline in effect at time of study conduct

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

TLF-11073

IUPAC Name:

TLF-11073

Details on test material:

- Purity: 22.82% solids in water

Test system

Details on study design:

Bovine corneas, obtained as a by-product from freshly slaughtered animals, were mounted in special holders and exposed to the test substance. An in vitro score was determined for the test substance based on the induction of opacity and permeability (to fluorescein) in the isolated bovine corneas. The positive control was ethanol and the negative control was sterile, deionized water. The test substance was administered to the test system without dilution.
Opacity measurement: Opacity was determined for each cornea using an Electro Design OP-KIT opacitometer. The change in opacity for each cornea (including the negative control corneas) was calculated by subtracting the initial opacity reading from the final opacity reading. These values were then corrected by subtracting from each the average change in opacity observed for the negative control corneas. The mean opacity value of each treatment group was calculated by averaging the corrected opacity values of each cornea for that treatment condition.
Permeability Measurement: The mean OD490 value for the blank wells was calculated. The mean blank OD490 value was then subtracted from the raw OD490 values of each well (corrected OD490). Any dilutions that were made to bring the OD490 readings into the linear range of the platereader (OD490 should be less than 1.500), had each diluted OD490 reading multiplied by the dilution factor. The final corrected OD490 value of the test substance and the positive control was then calculated by subtracting the average corrected OD490 value of the negative control corneas from the corrected OD490 value of each treated cornea. The mean OD490 value of each treatment group was calculated by averaging the final corrected OD490 values of the treated corneas for that treatment condition. The in vitro score was determined:
In Vitro Score = Mean Opacity Value + (15 x Mean OD490 Value).

Results and discussion

In vitro

Results

Irritation parameter:

in vitro irritation score

Value:

1.7

Vehicle controls validity:

valid

Positive controls validity:

not valid

In vivo

Irritant / corrosive response data:

Table 1 summarizes the opacity, permeability, and in vitro score for the test substance and positive control. Since the results of the positive control (ethanol) fell within two standard deviations of the historical mean (within a range of 39.2 to 64.0), the assay was considered valid.
Following the classification established by Gautheron et al. (1992) (Sina classification system) based on studies with a wide range of test materials, the test substance, would be considered a mild irritant. Following the modification of the Sina classification system proposed by Vanparys, et al. (1993) based on an evaluation of 50 pharmaceutical and commercially-available industrial compounds, the test substance would be considered a non-irritant.

Sina classification system
In vitro score:
from 0 to 25 = mild irritant
from 25.1 to 55 = moderate irritant
from 55.1 and above = severe irritant

Vanparys, et al modification of Sina classification system
In vitro score:
from 0 to 3 = non irritant
from 3.1 to 25 = mild irritant
from 25.1 to 55 = moderate irritant
from 55.1 and above = corrosive/severe irritant

Any other information on results incl. tables

Table 1 BCOP Results 

	Exposure time	Mean opacity value	Mean OD490 value	In vitro score	pH
Test substance	10 minutes	1.7	0.001	1.7	8.0
Positive control (Ethanol)	10 minutes	30.7	1.015	45.9

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
Non-irritant to eyes.

Executive summary:

The Bovine Corneal Opacity and Permeability Assay was used to assess the potential ocular irritancy of the test substance as measured by changes in opacity and permeability (to fluorescein) in isolated bovine corneas. Based on changes in corneal opacity and permeability (relative to the control corneas), an in vitro score was determined. The in vitro score was 1.7 Since the results of the positive control (ethanol) fell within two standard deviations of the historical mean (within a range of 39.2 to 64.0), the assay was considered valid. Following the classification established by Gautheron et al. (1992) (Sina classification system) based on studies with a wide range of test materials, the test substance, would be considered a mild irritant (in vitro score from 0 to 25). Following the modification of the Sina classification system proposed by Vanparys, et al. (1993) based on an evaluation of 50 pharmaceutical and commercially-available industrial compounds, the test substance would be considered a non-irritant (in vitro score from 0 to 3).