2-[4-(4-Alkoxyphenyl)-(pyridin-2-yl)-heteromonocyclyl]phenol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Study initiation date - 20 November 2020; Experiment start date - 21 November 2020; Experiment end date - 22 November 2020; Study completion date - 22 December 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 i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Test Item name: FAT 75637/B TE
Batch no.: AT-0063765400
Manufactured date: 21 April 2020
Expiry date: 27 May 2025
Storage condition: Ambient (+15 to +25 °C)
Physical Appearance: Light yellow powder
Solubility: Insoluble in water

Test animals / tissue source

Species:

cattle

Details on test animals or tissues and environmental conditions:

The bovine eyes were procured from local abattoir and transported in a jar containing Hank’s Balanced Salt Solution (HBSS) and penicillin-streptomycin (100 IU & 100 μg/mL) in an ice box.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

The positive control (Chlorhexidine) & test item (FAT 75637/B TE) were applied to the corneas as neat (quantity sufficient to cover entire corneal surface area), whereas negative control (Distilled water) was applied 0.75 mL to the each cornea.

Duration of treatment / exposure:

4 hours

Duration of post- treatment incubation (in vitro):

4 hours

Number of animals or in vitro replicates:

3 corneas/group

Details on study design:

SELECTION AND PREPARATION OF CORNEAS
- Procurement of corneas: The bovine eyes were procured from local abattoir and transported in a jar x containing Hank’s Balanced Salt Solution (HBSS) and penicillin-streptomycin (100 IU & 100 μg/mL) in an ice box. On day of experiment 25 numbers were found suitable for experiment.
- Dissection: On day of experiment, post pretest examination, eyes were dissected to isolate the corneas from surrounding tissue and then placed in a container of fresh HBSS (Hank Balanced Salt Solution).
- Mounting: The isolated corneas were mounted in the cornea holder, which separated holder into anterior and posterior chambers. During mounting, it was ensured that the epithelium of the cornea projected into the anterior chamber. The EMEM medium was added in to both the chambers and kept in an incubator (32 °C) for 1 hour.
- Opacity and Permeability: All the selected corneas for the study were tested for their opacity and permeability to calculate IVIS (In vitro irritancy score).

Results and discussion

In vitro

Results

Irritation parameter:

in vitro irritation score

Run / experiment:

Experiment 1

Value:

1.765

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Other effects / acceptance of results:

DEMONSTRATION OF TECHNICAL PROFICIENCY: Yes
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Yes
- Acceptance criteria met for positive control: Yes
The assay results are found to be accepted because the positive control i.e. Chlorhexidine used in this study has exhibited an IVIS score of 161.704 which fall between two standard deviations of the historical mean i.e 155-172.
Also, the negative control i.e. Distilled water response resulted in opacity and permeability values that are less than established upper limits for negative control opacity and permeability values.

Any other information on results incl. tables

Calculation of IVIS Score:

Treatment group	Mean Opacity value	Constant	Mean Permeability value	IVIS	Classification
Negative control (Distilled water)	0	15	0.0484	0.726	No Category
Chlorhexidine	133	15	1.9136	161.704	Category I
FAT 75637/B	2	15	-0.0157	1.765	No Category

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 75637/B referred as non eye irritant or as agent causing no serious eye damage, with the BCOP test method.

Executive summary:

The evaluation of the ocular irritancy of FAT 75637/B was carried out using the Bovine Corneal Opacity and Permeability assay. This study was conducted according to OECD test guideline 437 in a GLP-certified laboratory. Sufficient quantity to cover entire corneal surface area of the test item (FAT 75637/B) and positive control (Chlorhexidine) was applied to each cornea by means of open chamber method. A volume of 0.75 mL of negative control (Distilled water) were applied on the corneal surface by means of open chamber method. The control and treated corneas were then subjected to the opacity and permeability measurements. In this study, the negative control (Distilled water) was classified as UN GHS No Category (IVIS score 0.726) and the positive control (Chlorhexidine) was classified under Category 1 (IVIS score 161.704). The test item FAT 75637/B exhibited an IVIS score of 1.765 and was classified under UN GHS “No Category”. From the results, it can be concluded as the test item FAT 75637/B referred as non eye irritatant or as agent causing no serious eye damage, with the BCOP test method.