Benzamide, N,N-dibutyl-4-[4-(4-chlorophenyl)-2,3,5,6-tetrahydro-3,6-dioxopyrrolo[3,4-c]pyrrol-1-yl]-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November to December 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to OECD guideline under GLP

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

Not relevant

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

K-36

IUPAC Name:

K-36

Constituent 2

Reference substance name:

N,N-dibutyl-4-[4-(4-chlorophenyl)-3,6-dioxo-2H,3H,5H,6H-pyrrolo[3,4-c]pyrrol-1-yl]benzamide

Cas Number:

1391764-61-6

Molecular formula:

C27H28ClN3O3

IUPAC Name:

N,N-dibutyl-4-[4-(4-chlorophenyl)-3,6-dioxo-2H,3H,5H,6H-pyrrolo[3,4-c]pyrrol-1-yl]benzamide

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals / tissue source

Species:

other: Bos primigenius Taurus (Fresh bovine corneas)

Details on test animals or tissues and environmental conditions:

Fresh bovine corneas were held at 32 °C.

Test system

Vehicle:

other: olive oil

Amount / concentration applied:

750 μL of the test item suspension (concentration 20% in olive oil) were applied.

Duration of treatment / exposure:

Exposition time on the corneas was 4 h ± 5 min. at 32 °C.

Observation period (in vivo):

4 h ± 5 min.

Details on study design:

SCORING SYSTEM: IVIS (in vitro irritancy score)
TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Irritation parameter:

other: IVIS (in vitro irritancy score)

Basis:

mean

Time point:

other: 4

Score:

-0.182

Irritant / corrosive response data:

Physiological sodium chloride solution was used as negative control and olive oil was used as solvent control. The negative control and the solvent
control showed no irritating effect on the cornea and induced no serious eye damage.
20% Imidazole solution was used as positive control. The positive control induced serious eye damage on the cornea.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

The test item K-36 showed no irritating effects or serious eye damage on the cornea of the bovine eye. The calculated IVIS (in vitro irritancy score)
is -0.182. According to OECD Guideline no. 437 (Jul. 2013), a substance with an IVIS ≤ 3 requires no classification for eye irritation or serious eye
damage.

Executive summary:

This “in vitro” study was performed to assess the corneal damage potential of K-36 by quantitative measurements of changes in opacity and permeability in a bovine cornea. The study was performed for regulatory purposes.

One valid experiment was performed.

Bovine corneas were used. They were collected from slaughtered cattle which were between 12 and 60 months old.

The test item K-36 was brought onto the cornea of a bovine eye which had been incubated with cMEM without phenol red at 32 ± 1 °C for one hour and whose opacity had been measured. The test item was incubated on the cornea for 4 hours at 32 ± 1 °C. After removal of the test item, opacity and permeability values were measured.

Physiological sodium chloride solution was used as negative control and olive oil was used as solvent control. The negative control and the solvent control showed no irritating effect on the cornea and induced no serious eye damage.

20% Imidazole solution was used as positive control. The positive control induced serious eye damage on the cornea.

The test item K-36 showed no irritating effects or serious eye damage on the cornea of the

bovine eye. The calculated IVIS (in vitro irritancy score) is -0.182.