2,2'-[ethylenebis(oxyphenyl-2,1-eneazo)]bis[N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-3-oxobutyramide

Endpoint summary

Description of key information

Pigment Yellow 180 did not reveal any irritation potential on the skin of rabbits, tested in this study according to OECD test guideline no. 404 and GLP conditions.

Pigment Yellow 180 did not reveal any remarkable irritation potential on the eyes of rabbits,with standard methods regarding dosing, exposure duration, scoring system and reading time points. Therefore, it is concluded that the substance is not irritating to eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

From 15 OCT 2003 to 18 OCT 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD TG 404)

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Sandbach, Cheshire, UK
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2 to 3.5 kg
- Housing: Individually in suspended metal cages.
- Diet: certified rabbit diet (Code 5322, provided by International Product Supplies Limited, Wellingborough, UK); ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

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

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

water

Remarks:

distilled

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g/animal
VEHICLE
- Amount applied: 0.5 mL/animal

Duration of treatment / exposure:

4 h

Observation period:

3 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle swabbing with cotton wool soaked in 74% industrial methylated spirits
- 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 (beef redness) or eschar formation preventing grading of erythema...4

OEDEMA FORMATION
No oedema......................................................................................................................................0
Very slight oedema (barely perceptible)....................................................................................1
Slight oedema (edges of area well-defined by definite raising).............................................2
Moderate oedema (raised approximately 1 mm)............................................. ........................3
Severe oedema (raised more than 1 mm and extending beyond the area of exposure)...4

Irritation parameter:

erythema score

Basis:

animal: #1, #2, #3 each

Time point:

other: mean of 24, 48, 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Basis:

animal: #1, #2, #3 each

Time point:

other: mean of 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Other effects:

no signs of systemic toxicity, yellow staining at 1 and 24 h

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 skin of rabbits, tested in this study according to OECD test guideline no. 404 and GLP conditions.

Executive summary:

The primary skin irritation potential of the test item was investigated according to OECD test guideline no 404.The test item (0.5 g pasted with 0.5 ml of distilled water) was applied to the intact skin of three New Zealand White rabbits under semi-occlusive conditions for four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the test item.

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred. A light yellow staining was produced by the test item on the treated skin of the three male rabbits (1 -hour).

This persisted up to the 24-hour reading. A very slight erythema was noted in all animals at the 1 -hour and the 24 -hour reading (maximum score observed: 1), but was no longer present at the 48 -hour reading. Therefore, the overall erythema score in all animals was 0.33 and the overall edema score was 0.

Reference 2

Endpoint:

skin corrosion: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 09 JUN 1981 to 12 JUN 1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: FDA guideline (minor deviations from OECD guideline)

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: FDA guideline (Federal Register Vol. 38, nr. 187, p. 27019, 1973)

Deviations:

no

GLP compliance:

no

Remarks:

study was performed previous to GLP implementation

Species:

rabbit

Strain:

other: New Zealand

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: in-house breed collony
- Housing: single
- Diet: EKRA 8300, Futtermittelwerke Robert Koch oHG, Hamm, Germany), ad libitum
- Water: ad libitum

Vehicle:

other: polyethylenglycol 400

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg pasted in 0.23 ml polyethylenglycol 400

Duration of treatment / exposure:

24 h after exposure eyes were washed with physiological saline.

Observation period (in vivo):

72 h with observation time points at 1, 7, 24, 48 and 72 h after application.

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 h

SCORING SYSTEM: according to Draize Scale.

TOOL USED TO ASSESS SCORE: loupe / fluorescein (at 48 and 72 h reading)

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not relevant since no effect

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

other: not relevant since no effect

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: #1 and #4 each

Time point:

other: mean of 24, 48 and 72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: #2, #3 and #5 each

Time point:

other: mean of 24, 48 and 72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #6

Time point:

other: mean of 24, 48 and 72 h

Score:

0

Max. score:

3

Reversibility:

other: not relevant since no effect

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not relevant since no effect

Irritant / corrosive response data:

individual animal data at 1/7/24/48/72 h for animal #1-#6

cornea: 1/0/0/0/0, 0/0/0/0/0, 0/0/0/0/0,
0/0/0/0/0, 0/0/0/0/0, 0/0/0/0/0

iris: 1/0/0/0/0, 0/0/0/0/0, 0/0/0/0/0,
0/0/0/0/0, 1/0/0/0/0, 1/0/0/0/0

conjunctivae redness: 1/1/1/1/0, 1/1/1/0/0, 1/1/1/0/0,
1/1/1/1/0, 1/1/1/0/0, 1/0/0/0/0

chemosis: 1/0/0/0/0, 1/1/0/0/0, 1/0/0/0/0,
1/1/0/0/0, 1/1/0/0/0, 1/0/0/0/0

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 under test conditions which are basically in accordance with todays standard methods regarding dosing, exposure duration, scoring system and reading time points. Therefore, it is concluded that the submission substance is not irritating to eyes.

Executive summary:

Test material was subject to a test of eye irritancy according to FDA guidelines (Fed. Reg. Vol. 38, No. 187, p. 27019, 1973). 100 mg of substance pasted in polyethylenglycol were applied to one eye of six animals each. The eyes were washed 24 h after application and eye responses were noted for 72 h after start of the exposure. Only slight effects could be observed, conjunctiva redness score of 1 in 5/6 animals at the 24 h reading and in 2/6 animals at the 48 h reading. This effect was fully reversible within 72 h. Only slight other effects (iridial effects, score = 1 in 3/6 animals at the 1 h reading; Cornea score = 1 in 1/6 animals at 1 h reading; Chemosis score = 1 in 6/6 animals at the 1 h reading and in 3/6 animals at the 7 h reading) were observed after 1 and 7 h, these effects were reversible within 24 h.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

No calssification: No adverse effects observed.