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

Endpoint summary

Description of key information

Skin irritation was tested in a guideline study according to OECD guideline 404 in rabbits. 24 hours up to three days after treatment, the skin did not show any sign of erythema or edema. Mean scores on all observation time points after application were 0 for the three animals.

Pigmentadditive C was tested for its eye irritant properties in 3 New Zealand White rabbits.The study was performed according to OECD Guideline 405. 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.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Oct 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

Adopted 12 May 1981

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

25. April 1984

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, Kastengrund, Germany; conventional breed
- Age at study initiation: 3 - 5 months
- Weight at study initiation: 2.8 - 3.4 kg
- Housing: individual in 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: 3.10. To: 6.10.1989

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: applied as paste in polyethylene glycol 400

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
500 mg

VEHICLE
- Amount(s) applied (volume or weight with unit):
0.5 mL
- Concentration (if solution):
n.a. paste

Duration of treatment / exposure:

4 h
Then test substance was removed from the skin with warm tap water.

Observation period:

30 - 60 min. after removal of the patches
24, 48 and 72 hrs after removal of the patches

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: 100%
The moistened substance was applied over the whole surface of a 2.5 x 2.5 cm cellulose patch on a piece of surgical plaster (specially produced by Beiersdorf AG, Hamburg). The plaster was fixed to the prepared skinarea (ca. 25 cm2) and then covered with a semi-occlusive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with warm tap water
- Time after start of exposure: 4 h

SCORING SYSTEM:

Erythema and eschar formation
No erythema.......................................................................................................................0
very slight erythema (barely perceptible)......................................................................1
well-defined erythema......................................................................................................2
moderate to severe erythema..........................................................................................3
severe erythema (beet redness) to slight eschar formation (lesion in depth).........4

Oedema
No oedema...................................................................................................................................0
very slight oedema (barely perceptible)..................................................................................1
slight oedema (edges of area well defined by definite raising)............................................2
moderate oedema (raised approximately 1mm)....................................................................3
severe oedema (raised more than 1mm and extending beyond area of exposure.........4

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No erthema/edema recorded

Other effects:

1 hour after removal of the patches, the treated skin of the animals was discoloured yellow. No signs of skin irritation were observed at any time during the study.

Interpretation of results:

GHS criteria not met

Conclusions:

No edema or erythema were recorded after 4 h exposure of 500 mg test item to rabbit skin. Therefore, the test substance is considered to be not irritating.

Executive summary:

Skin irritation was tested in a guideline study according to OECD guideline 404 in rabbits.30 min up to three days after treatment, the skin did not show any sign of erythema or edema. Mean scores on all observation time points after application were 0 for the three animals.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

Adopted 24. Feb. 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

25. April 1984

Deviations:

no

GLP compliance:

yes

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

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

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

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.8

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.8

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation: 1 key study available: not irritating

Eye irritation: 1 key study available: irritating

 

There is one reliable study on the skin irritancy potential. Skin irritation was tested in a guideline study according to OECD guideline 404 in 3 New Zealand White rabbits. 24 hours up to three days after treatment, the skin did not show any sign of erythema or edema. Mean scores on all observation time points after application were 0 for the three animals.

There is one reliable study available on the eye irritancy potential. The test item was tested for its eye irritant properties in 3 New Zealand White. This study was performed according to OECD Guideline 405. 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.

Justification for classification or non-classification

With reference the reported scores Pigmentadditive C does not have to be classified as irritant to the skHPP Additive D11in according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

With reference the reported scores and reversibility of effects the test substance has to be classified as irritant to the eyes, cat. 2 (H318 - Causes serious eye irritation) according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).