4-[(2,5-dichlorophenyl)azo]-N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-3-hydroxynaphthalene-2-carboxamide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD TG 405) performed under GLP

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:

4-[(2,5-dichlorophenyl)azo]-N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-3-hydroxynaphthalene-2-carboxamide

EC Number:

230-258-1

EC Name:

4-[(2,5-dichlorophenyl)azo]-N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-3-hydroxynaphthalene-2-carboxamide

Cas Number:

6992-11-6

Molecular formula:

C24H15Cl2N5O3

IUPAC Name:

4-[(1E)-2-(2,5-dichlorophenyl)diazen-1-yl]-3-hydroxy-N-(2-oxo-2,3-dihydro-1H-1,3-benzodiazol-5-yl)naphthalene-2-carboxamide

Test material form:

solid: nanoform, no surface treatment

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: 12-15 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. 85/05; 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:

single application, the treated eyes were not rinsed after instillation

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3 (1 male, 2 females)

Details on study design:

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

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

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:

other: reversibility not applicable

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 and #2 each

Time point:

other: mean of 24-48-72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility not applicable

Results 4

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

other: mean of 24-48-72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24-48-72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritant / corrosive response data:

The mean score was calculated across 3 scoring times (24, 48 and72 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 0.00,0.00 and 1.00 for reddening and 0.00 for chemosis for all animals, respectively. Very slight corneal opacity affecting the whole area was noted in all treated animals 1 hour after instillation but was no langer present at the 24-hour reading. No abnormal findings were noted in the iris of any of the animals.
Slight reddening of the conjunctivae was noted in all animals one hour after treatment and persisted until the 72-hour reading in one animal.
Slight reddening of the sclerae was noted in one animal from 1 hour after treatment to the 72-hour observation.
Slight ocular discharge was noted in all animals at the 1-hour reading.
No abnormal findings were observed in the treated eye of any animal7 days after treatment.

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test item did not induce significant or irreversible damage to the rabbit eye in this study according to OECD test guideline no. 405 and GLP conditions.

Executive summary:

The eye irritating potential of the test item was assessed according to OECD TG 405. Three rabbits were exposed to 0.1 mg test item. The mean score was calculated across 3 scoring times (24, 48 and72 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 0.00,0.00 and 1.00 for reddening and 0.00 for chemosis for all animals, respectively. Very slight corneal opacity affecting the whole area was noted in all treated animals 1 hour after instillation but was no langer present at the 24-hour reading. No abnormal findings were noted in the iris of any of the animals.

Slight reddening of the conjunctivae was noted in all animals one hour after treatment and persisted until the 72-hour reading in one animal.

Slight reddening of the sclerae was noted in one animal from 1 hour after treatment to the 72-hour observation.

Slight ocular discharge was noted in all animals at the 1-hour reading.

No abnormal findings were observed in the treated eye of any animal 7 days after treatment.