Dimethyl 5-[[1-[[(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)amino]carbonyl]-2-oxopropyl]azoterephthalate

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 24 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:

Dimethyl 5-[[1-[[(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)amino]carbonyl]-2-oxopropyl]azoterephthalate

EC Number:

249-955-7

EC Name:

Dimethyl 5-[[1-[[(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)amino]carbonyl]-2-oxopropyl]azoterephthalate

Cas Number:

29920-31-8

Molecular formula:

C21H19N5O7

IUPAC Name:

dimethyl 5-({2-oxo-1-[(2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)carbamoyl]propyl}diazenyl)isophthalate

Test material form:

solid: nanoform

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: 10-14 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:

7 days (single application, the treated eyes were not rinsed after application)

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3 (1 male, 2 females)

Details on study design:

SCORING SYSTEM: Reading was done at time point 1, 7, 24, 48 and 72 h as well as 7 days.
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:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Results 4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable

Results 5

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal: #1 and #2 each

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 6

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 7

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Results 8

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritant / corrosive response data:

Individual animal data for animal #1, #2, #3 at time point 1h / 24h / 48h / 72 h / 7 days

cornea score: 1/0/0/0/0, 1/1/0/0/0, 1/0/0/0/0
iris score: 0/0/0/0/0, 0/0/0/0/0, 0/0/0/0/0
conjunctivae redness: 1/1/1/1/0, 1/1/1/1/0, 1/1/0/0/0
chemosis: 1/0/0/0/0, 1/0/0/0/0, 0/0/0/0/0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Regulation (EC) no 1272/2008

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 primary eye irritation potential of the test item was investigated according to OECD test guideline no 405.The test item was applied by instillation of 0.1 g into the left eye of each of three young New Zealand White rabbits. The scoring of irritating effects was performed 1, 24, 48 and 72 hours as well as 7 days after test item instillation.

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 were 0.00, 0.33 and 0.00 for the three animals. The individual mean score for iris was 0.00 for all three animals. The individual mean scores for the conjunctivae were 1.00, 1.00 and 0.33 for reddening, respectively and 0.00 for chemosis for each of the three animals. A slight corneal opacity affecting the whole area was observed in the treated eyes of all three animals 1 hour after the instillation and was still present in one animal at the 24-hour reading. Slight reddening of the conjunctivae was noted in all three animals from the 1-hour reading on and persisted up to the 24- or 72-hour reading. A slight swelling of the conjunctivae was observed in two animals 1 hour after instillation. Slight reddening of the sclerae was present in all three animals one hour after the instillation and persisted up to the 24-, 48- or 72-hour reading. Slight ocular discharge was observed in all three animals 1 hour after the treatment and still at the 24-hour reading in one animal. Remnants of the test item were noted in the treated eyes of the three animals 1 hour after test item instillation and still at the 24- and 48-hour readings in one animal. No abnormal findings were observed in the treated eye of any animal 7 days after treatment, the end of the observation period for all animals. No corrosion of the cornea was observed at any of the reading times.