N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-2-[(2-methoxyphenyl)azo]-3-oxobutyramide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 12 JUL 2006 to 20 JUL 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD TG 405)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-2-[(2-methoxyphenyl)azo]-3-oxobutyramide

EC Number:

279-914-9

EC Name:

N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-2-[(2-methoxyphenyl)azo]-3-oxobutyramide

Cas Number:

82199-12-0

Molecular formula:

C18H17N5O4

IUPAC Name:

2-[(1E)-2-(2-methoxyphenyl)diazen-1-yl]-3-oxo-N-(2-oxo-2,3-dihydro-1H-1,3-benzodiazol-5-yl)butanamide

Test material form:

solid: bulk

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan Netherlands BV, Horst, The Netherlands
- Age at study initiation: 11-14 weeks
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet (batch no. 24/06; provided by Provimi Kliba AG, CH-4303 Kaiseraugst); ad libitum
- Water: Community tap water from Füllinsdorf, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 g

Duration of treatment / exposure:

72 h (single application / treated eyes were not rinsed after instillation)

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

3 (1 male, 2 females)

Details on study design:

SCORING SYSTEM:
Grading of Ocular Lesions according to COMMISSION DIRECTIVE 2004/73/EC, APRIL 29, 2004; comparable to Draize system

CORNEA
Opacity: degree of density (area most dense taken for reading)
No ulceration or opacity.......................................................................................................0
Scattered or diffuse areas of opacity (other than slight dulling of normal
luster), details of iris clearly visible.....................................................................................1
Easily discernible translucent area, details of iris slightly obscured.............................2
Nacreous area, no details of iris visible, size of pupil barely discernible......................3
Opaque cornea, iris not discernible through the opacity................................................4

IRIS
Normal.....................................................................................................................................0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal
hyperemia, or injection, any of these or combination of any thereof, iris still
reacting to light (sluggish reaction is positive).................................................................1
No reaction to light, hemorrhage, gross destruction (any or all of these)...................2

CONJUNCTIVAE
Redness (refers to most severe reading of palpebral and bulbar conjunctivae
when compared with control eye)
Blood vessels normal..............................................................................................................0
Some blood vessels definitely hyperemic (injected)..........................................................1
Diffuse, crimson color, individual vessels not easily discernible....................................2
Diffuse beefy red......................................................................................................................3

Chemosis: lids and/or nictitating membranes
No swelling................................................................................................................................0
Any swelling above normal (including nictitating membranes)........................................1
Obvious swelling with partial eversion of lids.....................................................................2
Swelling with lids about half-closed......................................................................................3
Swelling with lids more than half-closed..............................................................................4

TOOL USED TO ASSESS SCORE:
Eye examinations were made with a Varta Cliptrix diagnostic-lamp (Roth AG, Reinach/Switzerland).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24-48-72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 h

Remarks on result:

other: at the 1 hour reading very slight opacity affecting the whole area in 2 animals

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24-48-72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable

Results 3

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

other: mean of 24-48-72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Results 4

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

other: mean of 24-48-72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible

Remarks:

72 h

Results 5

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

other: mean of 24-48-72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible

Remarks:

72 h

Results 6

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24-48-72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item did not reveal any remarkable irritation potential on the eyes of rabbits, tested in this study according to OECD test guideline no. 405 and GLP conditions.

Executive summary:

The test item was applied by instillation of 0.1 g into the left eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test item instillation. The instillation of the test item into the eye resulted in mild, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae. These effects were reversible and were no longer evident 72 houres after treatment, the end of the observation period for all animals. In two animals a slight corneal opacity affecting the whole area was noted at the 1-hour reading but was no longer present on the following day.

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctivae were 0.67, 0.67 and 0.33 for reddening and 0.00 for chemosis for all animals, respectively.

No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was observed and no clinical signs were observed.