2-(4-(diethylaminopropylcarbamoyl)phenylazo)-3-oxo-N-(2,3-dihydro-2-oxobenzimidazol-5-yl)butyramide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Oct -Nov 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

Adopted 24. Feb. 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

25. April 1984

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-(4-(diethylaminopropylcarbamoyl)phenylazo)-3-oxo-N-(2,3-dihydro-2-oxobenzimidazol-5-yl)butyramide

EC Number:

404-910-2

EC Name:

2-(4-(diethylaminopropylcarbamoyl)phenylazo)-3-oxo-N-(2,3-dihydro-2-oxobenzimidazol-5-yl)butyramide

Cas Number:

164578-14-7

Molecular formula:

C25H31N7O4

IUPAC Name:

N-[3-(diethylamino)propyl]-4-[(1E)-2-{2-oxo-1-[(2-oxo-2,3-dihydro-1H-1,3-benzodiazol-5-yl)carbamoyl]propyl}diazen-1-yl]benzamide

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: Hoechst AG, Kastengrund, Germany (convential breed)
- Age at study initiation: 3-5 months
- Weight at study initiation: 3.0 - 3.5 kg
- Housing: in fully air-conditioned rooms, separate cages (arranged in a battery)
- Diet (e.g. ad libitum): Altromin 2123 maintenance diet - rabbits (Altromin GmbH, Lage/Lippe), ad libitum and hay (approx. 15 g daily)
- Water (e.g. ad libitum): deionised, chlorinated water from automatic water dispenser, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/-3°C
- Humidity (%): 50+/-20%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 31.10. To: 3.11.1989

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

100 mg

Duration of treatment / exposure:

24 h

Observation period (in vivo):

The eyes were examined 1, 24, 48 and 72 hours, 7 days after application of the test substance.
At 24 and 72 hours the eyes were also examined for corneal lesions under UV light after instillation of one drop of 0.01 % fluorescein-sodium solution. Lesions in cornea, iris or conjunctivae were graded numerically.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): 24 hours after application and at all other designated examination times at which the treated eyes still showed discharge or at which a corneal examination with fluorescein-sodium solution took place, the treated eyes were washed out thoroughly with physiological saline at approx. 37 °C.


SCORING SYSTEM:

CORNEA
Degree of opacity (most dense area used)
No opacity ...................................................................................................................0
Scattered or diffuse areas, details of iris clearly visible........................................1
Easily discernible translucent areas, details of iris slightly obscured................2
Opalescent areas, no details of iris visible , size of pupil barely discernible ....3
Opaque, iris invisible ..................................................................................................4

Affected area (Opactiy and fluorescein-test)
0 = no translucence
1 = punctiform up to 1/4
2 = more than 1/4 up to 1/2
3 = more than 1/2 up to 3/4
4 = more than 3/4 up t o 4/4

IRIS
Normal ......................................................................................................................... 0
Folds above normal , congestion, swelling, circumcorneal injection (any of all of these or combination of any thereof); iris still reacting to light
(sluggish reaction is positive) ......................... .........................................................1
No reaction to light, haemorrhage, gross destruction (any or all of these) ......2


CONJUNCTIVAE

Redness (refers to palpebral and bulbar conjunctivae)
Blood vessels normal...............................................................................................................0
Blood vessels definitely injected above normal ................................................................. 1
More diffuse, deeper crimson red, individual blood vessels not easily discernible .....2
Diffuse beefy red......................................................................................................................3

Chemosi s (refers to palpebral and bulbar conjunctivae)
No swelling .........................................................................................0
Any swelling above normal (includes nictitating membran) ..... 1
Obvious swelling with partial eversion of l i d s ...........................2
Swelling with lids about half closed ................................................3
Swelling with lids half closed to completely closed.......................4
TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.1

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 h

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.8

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.8

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible

Irritant / corrosive response data:

Redness and swelling of the lid was observed 1 and 24 h after substance application. Additionally diffuse opcatiy of the cornea and discharge colored by the substance was reported in one animal. 24 h after substance application the iris of all animals was reddened. Two animals showed slight chemosis. These symptoms dissappeared by 3 days.
The test substance is slightly irritating.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

With reference the reported scores (reversibility of effects) Pigmentadditive C has to be classified as irritant to the eyes Cat. 2 according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

Executive summary:

Redness and swelling of the lid was observed 1 and 24 h after substance application. Additionally diffuse opcatiy of the cornea and discharge colored by the substance was reported in one animal. 24 h after substance application the iris of all animals was reddened. Two animals showed slight chemosis. These symptoms dissappeared by 3 days.

The test substance is slightly irritating.