2-[4-(1-hydroxy-4-{4-[hydroxy(diphenyl)methyl]piperidin-1-yl}butyl)phenyl]-2-methylpropanenitrile

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:

2016

Report date:

2016

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 Ocular Corrosives and Severe Irritants)

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)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-(4-{1-hydroxy-4-[4-(hydroxydiphenylmethyl)piperidin-1-yl]butyl}phenyl)-2-methylpropanenitrile

EC Number:

811-752-1

Cas Number:

169032-19-3

Molecular formula:

C32 H38 N2 O2

IUPAC Name:

2-(4-{1-hydroxy-4-[4-(hydroxydiphenylmethyl)piperidin-1-yl]butyl}phenyl)-2-methylpropanenitrile

Test animals / tissue source

Species:

cattle

Test system

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

0.75 g of test article was applied to the corneas.

Duration of treatment / exposure:

4 hours

Duration of post- treatment incubation (in vitro):

1.5 hours (after the addition of fluorescein solution)

Number of animals or in vitro replicates:

3 corneas per groups (test article, positive and negative controls)

Details on study design:

After the incubation of the test article on the corneas, each cornea was washed with media containing phenol red followed by media without phenol red and the corneas assessed for opacity.
For the permeability endpoint, sodium fluorescein solution was added into the anterior chamber and the corneas were incubated in the vertical position for 1.5 hours at 32°C. Following this period, the media in the posterior chamber was removed and three 350 µL aliquots of this media (per cornea) were analysed for optical density at 490 nanometers.
A volume of 750 µL of the negative and positive control was similarly applied to further groups of three corneas.

Results and discussion

In vitro

Results

Results 1

Irritation parameter:

in vitro irritation score

Value:

ca. 9.09

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: no prediction can be made in respect of its potential to cause eye irritation

Results 2

Irritation parameter:

cornea opacity score

Run / experiment:

mean

Value:

ca. 9

Negative controls validity:

valid

Positive controls validity:

valid

Results 3

Irritation parameter:

other: optical density

Run / experiment:

mean

Value:

ca. 0.006

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

The assay was considered valid as the assay acceptance criteria were met.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

It was concluded that 2-[4-[1-hydroxy-4-[4-[hydroxy(diphenyl)methyl]-1-piperidyl]butyl]phenyl]-2-methyl-propanenitrile produced an IVIS (in vitro irritation score) score of 9.09 (> 3 and =< 55). As a consequence, no prediction can be made in respect of its potential to cause eye irritation.