N-{[1,1'-Biphenyl]-2-yl}-N-(9,9-dimethyl-9H-fluoren-2-yl)-7'-phenyl-9,9'-spirobi[fluoren]-7-amine

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Nov 01 - Dec 11, 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

Test guideline 1

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:

2017

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)

Version / remarks:

Commission Regulation (EU) 2017/735 of 14 February 2017 amending, for the purpose of its adaption to technical progress, the Annex to Regulation (EC) No 440/2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

N-{[1,1'-biphenyl]-3-yl}-N-(9,9-dimethyl-9H-fluoren-2-yl)-7'-phenyl-9,9'-spirobi[fluoren]-7-amine

EC Number:

949-957-4

Cas Number:

2423014-10-0

Molecular formula:

C58H41N

IUPAC Name:

N-{[1,1'-biphenyl]-3-yl}-N-(9,9-dimethyl-9H-fluoren-2-yl)-7'-phenyl-9,9'-spirobi[fluoren]-7-amine

Test material form:

solid

Specific details on test material used for the study:

PREPARATION OF THE TEST MATERIAL
The test item was prepared as a 20% (w/v) solution in a 0.9% sodium chloride solution. The stability in the vehicle was not investigated. The test item preparation was administered within <1 hour after preparation.

Test system

Vehicle:

physiological saline

Controls:

yes, concurrent vehicle

yes, concurrent positive control

Amount / concentration applied:

TEST MATERIAL: 750 µL (i.e. 150mg/750µL)

NEGATIVE / VEHICLE CONTROL: 750 µL

Designation: 0.9% sodium chloride solution
Supplier: B. Braun Melsungen AG, Germany
Batch: 17361013
Storage: 2 to 8°C
Released until: August 2020


POSITIVE CONTROL: 750 µL

Designation: Art. 814223
Synonym: Imidazole
Supplier: Merck KGaA, Germany
Batch: S5798623
Purity (GC) 99.8% (a/a)
Storage: At room temperature
Released until: April 30, 2023

Imidazole was dissolved with 0.9% sodium chloride solution to a concentration of 20% (w/v).

Duration of treatment / exposure:

240 minutes

Number of animals or in vitro replicates:

in vitro: triplicate design

Results and discussion

In vitro

Results

Irritation parameter:

in vitro irritation score

Run / experiment:

Run 1 / Experiment 1

Value:

5.8

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

not determinable

Remarks:

According to OECD 437 no prediction can be made regarding the eye hazard potential of the test item.

Other effects / acceptance of results:

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: After treatment with the negative control (0.9% sodium chloride solution) the calculated IVIS was 0.1 and, thus, within three standard deviations of the current historical mean of the negative control (IVIS: -1.4 – 3.1).
- Acceptance criteria met for positive control: After treatment with the positive control (20% Imidazole) the calculated IVIS was 117.0 and, thus, also within two standard deviations of the current historical mean of the positive control (IVIS: 82.3 – 132.4).

Therefore, the study fulfilled the acceptance criteria.

Any other information on results incl. tables

Results

The IVIS obtained after treatment with the test material was 5.8 and, thus higher than 3 and lower than 55, i.e. according to OECD 437 no prediction can be made regarding the eye hazard potential of the test item.

The results are given in the following table:

		Opacity	Permeability	IVIS
				per cornea	per group (mean value)	Standard deviation
Negative control	0.9% sodium chloride solution	0.0	-0.001	-0.015	0.1	0.4
		0.6	-0.003	0.555
		-0.1	-0.002	-0.130
Positive control	Imidazole (20%)	68.44	1.928	97.320	117.0	17.1
		86.2	2.630	125.650
		70.4	3.846	128.090
Test item	Test material preparation	4.6	-0.001	4.585	5.8	4.4
		2.1	-0.002	2.070
		10.7	-0.001	10.685

No observations (e.g. tissue peeling, residual test chemical, non-uniform opacity patterns) were seen in a visually inspection of the corneas after treatment.

Study Acceptance Criteria

After treatment with the negative control (0.9% sodium chloride solution) the calculated IVIS was 0.1 and, thus, within three standard deviations of the current historical mean of the negative control (IVIS: -1.4 – 3.1). After treatment with the positive control (20% Imidazole) the calculated IVIS was 117.0 and, thus, also within two standard deviations of the current historical mean of the positive control (IVIS: 82.3 – 132.4). Therefore, the study fulfilled the acceptance criteria.
The resulting classification of the test item in this study is unequivocal and no borderline results were obtained. Therefore, a single testing run composed of three corneas per group was considered sufficient.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

Under the conditions of the present study, the eye hazard potential of the test item cannot be predicted.

Executive summary:

This study was performed according to GLP and the methods applied are fully compliant with OECD TG 437. Under the conditions of the present study, the eye hazard potential of the test item cannot be predicted.