Fenspiride

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

april 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

This test is designed to measure the opacity of the cornea by quantifying the ability of light to pass through it. The permeability, as a result of the irritation potential of the test item, is determined using Na-fluorescein solution. The comparison of the opacity before and after the
exposure to the test item and the determination of the permeability after the treatment provide an indication of the damaging effect of the test item.
For this purpose the induction of opacity and increased permeability in an isolated bovine cornea after application of the test item was measured. The results of both criteria were combined. The resulting in vitro irritation factor was compared with the classification “no Category (GHS)”, “no prediction can be made”, and "serious eye damaging" (CLP/EPA/GHS (Cat 1)).
The purpose of this study was to assess the possible corneal damage potential when fresh bovine corneae are exposed to the test item.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

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)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Fenspiride

EC Number:

225-751-3

EC Name:

Fenspiride

Cas Number:

5053-06-5

Molecular formula:

C15H20N2O2

IUPAC Name:

8-(2-phenylethyl)-1-oxa-3,8-diazaspiro[4.5]decan-2-one

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Batch: 18115637

Test animals / tissue source

Species:

cattle

Details on test animals or tissues and environmental conditions:

Freshly isolated bovine eyes of at least 9 month old donor cattle were collected from the
abattoir. Excess tissue was removed from the excised eyes. The isolated eyes were stored in
HBSS containing 1% (v/v) Penicillin/Streptomycin (100 units/mL penicillin and 100 μg/mL
streptomycin) in the cooled slaughter-house until transportation on the same morning to the
laboratory using a Styrofoam box. The corneae were isolated on the same day after delivery
of the eyes.

Test system

Vehicle:

physiological saline

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

20% (w/v) suspension in saline (0.9% (w/v) NaCl in deionised water) of the test item 428 BASE BRUTE

Duration of treatment / exposure:

240 minutes

Duration of post- treatment incubation (in vitro):

90 minutes

Results and discussion

In vitro

Results

Irritation parameter:

in vitro irritation score

Value:

ca. 22.48

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Any other information on results incl. tables

After a first opacity measurement of the fresh bovine corneae (t0), the 20% (w/v) suspension in saline (0.9% (w/v) NaCl in deionised water) of the test item 428 BASE BRUTE, the positive and the negative controls were applied to corneae fixed in an incubation chamber in horizontal position and incubated for 240 minutes at 32 ± 1 °C. The posterior chamber contained incubation medium. After the incubation phase the test item, the positive, and the negative controls were each rinsed from the corneae and opacity was measured again (t240). After the opacity measurements permeability of the corneae was determined by measuring spectrophotometrically the transfer of sodium fluorescein after incubation in a horizontal position for 90 minutes at 32 ± 1 °C.

With the negative control (physiological saline) neither an increase of opacity nor permeability of the corneae could be observed.

The positive control (10% (w/v) Benzalkonium chloride in saline) showed clear opacity and distinctive permeability of the corneae corresponding to a classification as serious eye

damage (CLP/EPA/GHS (Cat 1)).

Relative to the negative control, the test item 428 BASE BRUTE caused an increase of the corneal opacity and permeability. The calculated mean in vitro irritancy score was 22.48.

According to OECD 437 (see table in chapter 3.8.3) the test item is not classified as serious eye damaging (CLP/EPA/GHS (Cat 1) but the test item’s hazard for eye damaging cannot be predicted.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Relative to the negative control, the test item 428 BASE BRUTE caused an increase of the corneal opacity and permeability. The calculated mean in vitro irritancy score was 22.48.
According to OECD 437 (see table in chapter 3.8.3) the test item is not classified as serious eye damaging (CLP/EPA/GHS (Cat 1) but the test item’s hazard for eye damaging cannot be predicted.