7,17,28,38-tetraazatridecacyclo[24.16.2.2²,⁵.1⁸,¹².1²⁹,³³.0³,²².0⁴,¹⁹.0⁶,¹⁷.0²³,⁴³.0²⁷,³⁸.0⁴⁰,⁴⁴.0¹⁶,⁴⁶.0³⁷,⁴⁵]octatetraconta-1(42),2(48),3,5(47),6,8,10,12(46),13,15,19,21,23,25,27,29(45),30,32,34,36,40,43-docosaene-18,39-dione; 7,17,28,38-tetraazatridecacyclo[24.16.2.2²,⁵.1⁸,¹².1²⁹,³³.0³,²².0⁴,¹⁹.0⁶,¹⁷.0²³,⁴³.0²⁸,³⁹.0⁴⁰,⁴⁴.0¹⁶,⁴⁶.0³⁷,⁴⁵]octatetraconta-1(42),2(48),3,5(47),6,8,10,12(46),13,15,19,21,23,25,29,31,33,35,37(45),38,40,43-docosaene-18,27-dione

Endpoint summary

Description of key information

Skin irritation/corrosion: non-irritating, according OECD TG 404, GLP-compliant, 0.5 g test substance, semiocclusive, 4 h, rabbit, 2005, K1
Eye Irritation: non-irritating, according OECD TG 405, GLP-compliant, 0.1 mL test substance, 1 h, rabbit, 2005, K1

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:

Aug. 08, 2005 - Sep. 14, 2005

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 April 24, 2002

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

- Physical state: Powder / black
- Storage condition of test material: Room temperature
- Expiration date of the lot/batch: unlimited at room temperature
- Analytical purity: 99.9%

Species:

rabbit

Strain:

New Zealand White

Remarks:

A 1077 INRA (SPF)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Centre Lago S.A., 01540 Vonnas, France
- Age at study initiation: 8 - 9 months
- Weight at study initiation: 3.02 kg - 4.16 kg
- Housing: Individually in stainless steel wire mesh cages with grating, floor area: 3000 cm2
- Diet: Kliba-Labordiät (Kaninchen & Meerschweinchenhaltung "GLP"), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland (about 130 g/animal per day)
- Water: Tap water ad libitum
- Acclimation period: At least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 30- 70%
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: Feb. 01, 2005 (Arrival of the animals) To: Aug. 15, 2005 (Day of last observation)

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: minimally moistened with a suitable amount of doubly-distilled water

Controls:

other: untreated skin of the same animals served as control

Amount / concentration applied:

TEST MATERIAL:
- Amount(s) applied (volume or weight with unit): The solid test substance was minimally moistened with a suitable amount of doubly-distilled water to guarantee skin contact immediately before test substance application (corresponding to a dose of 0.5 g of unchanged test substance). Because of the natural moisture of the skin doubly-distilled water was used for moistening, so that the test was carried out under conditions as physiological as possible.

Duration of treatment / exposure:

4 h

Observation period:

7 days

Number of animals:

3 (2 males, 1 female animal)

Details on study design:

TEST SITE
- Area of exposure: flank
- Type of wrap if used: The test substance was covered with a test patch (2.5 x 2.5 cm) Idealbinde, Pfälzische Verbandstoff-Fabrik, Kaiserslautern) and Fixomull stretch (adhesive fleece), Beiersdorf AG

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test substance was removed at the end of the exposure period with LutroI and Lutrol / water (1: 1).
- Time after start of exposure: 4 h

SCORING SYSTEM: according to OECD 404

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Scaling at the end of the observation period (7 days)

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Irritant / corrosive response data:

Slight or moderate erythema was observed in the animals during the course of the study.

The application area was slight black discolored in two animals during the observation period. Scaling was noticed in one animal at study termination, only.

The cutaneous reactions, with the exception of scaling, were reversible in all animals within 7 days after removal of the patch at latest.

The average score (24 to 72 hours) for irritation was calculated to be 1.2 for erythema and 0.0 for edema.

Exposition:	4 h (semiocclusive)
Animal	Reading	Erythema	Edema	Comments
1	0 h	1	0
2	0 h	2	0	Application area slight black discolored
3	0 h	2	0	Application area slight black discolored
1	1 h	2	0
2	1 h	2	0	Application area slight black discolored
3	1 h	2	0	Application area slight black discolored
1	24 h	1	0
2	24 h	2	0	Application area slight black discolored
3	24 h	2	0	Application area slight black discolored
1	48 h	1	0
2	48 h	2	0	Application area slight black discolored
3	48 h	1	0	Application area slight black discolored
1	72 h	0	0	Study discontinued because the animal was free of findings
2	72 h	2	0	Application area slight black discolored
3	72 h	0	0	Study discontinued because the animal was free of findings
2	7 days	0	0	Scaling
mean (animal 1)	24 - 72 h	0.7	0
mean (animal 2)	24 - 72 h	2	0
mean (animal 3)	24 - 72 h	1	0
mean (animal 1-3)	24 - 72 h	1.2	0

Interpretation of results:

GHS criteria not met

Conclusions:

Considering the described cutaneous reactions as well as the average score for irritation, the test substance shows a slight skin irritation potential below the regulatory threshold under the test conditions chosen.

Executive summary:

The test article's potential to cause acute dermal irritation or corrosion was assessed by a GLP-compliant study according to OECD guideline 404. An amount of 0.5 g of the test substance was applied topically for 4 hours to the intact skin of three White New Zealand rabbits, using a patch of 2.5 cm x 2.5 cm, covered with semiocclusive dressing. After removal of the patch the application area was washed off. The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch and on day 7. Slight or moderate erythema was observed in the animals during the course of the study. The application area was slight black discolored in two animals during the observation period. Scaling was noticed in one animal at study termination, only. The cutaneous reactions, with the exception of scaling, were reversible in all animals within 7 days after removal of the patch at latest. The average score (24 to 72 hours) for irritation was calculated to be 1.2 for erythema and 0.0 for edema. Therefore, under the test conditions chosen, the test article is considered to be non irritating according to GHS and EU regulations.

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:

Aug. 23, 2005 - Sep. 14, 2005

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 April 24, 2002

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

- Physical state: Powder / black
- Storage condition of test material: Room temperature
- Analytical purity: 99.9%
- Expiration date of the lot/batch: unlimited at room temperature

Species:

rabbit

Strain:

New Zealand White

Remarks:

A 1077 INRA (SPF)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Centre Lago S.A., 01540 Vonnas, France
- Age at study initiation: 2 - 3 months
- Weight at study initiation: 2.23 kg - 2.34 kg
- Housing: Individually in stainless steel wire mesh cages with grating, floor area: 3000 cm2
- Diet (e.g. ad libitum): Kliba-Labordiät (Kaninchen & Meerschweinchenhaltung "GLP"), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland (about 130 g/animal per day)
- Water: Tap water ad libitum
- Acclimation period: At least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 30 - 70%
- Air changes (per hr): Fully air-conditioned rooms with a central air-conditioning system
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: Aug. 17, 2005 (arrival of the animals) To: Sep. 01, 2005 (Day of last observation)

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated left eye

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL bulk volume (about 16 mg of the comminuted test substance)

Duration of treatment / exposure:

1 h

Observation period (in vivo):

9 days

Number of animals or in vitro replicates:

3 animals (2 males, 1 female animal)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): About 1 hour after application of the solid test substance the treated eye of the animal(s) was rinsed with 3 to 6 mL of hand warm tap water for 1 to 2 minutes using a syringe with a blunt probe.
- Time after start of exposure: 1 h

SCORING SYSTEM: according to OECD 405

TOOL USED TO ASSESS SCORE: Daylight tubes "Lumilux" (L 58W/860 PLUS ECO 25X1, Osram, Germany)

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effects

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: Two animals showed injected scleral vessels in a circumscribed area (reversible within 24 - 48 h)

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Irritant / corrosive response data:

Slight to moderate conjunctival redness, slight conjunctival chemosis and slight discharge were observed in the animals up to 24 hours after application.

Two animals showed injected scleral vessels in a circumscribed area.

The ocular reactions were reversible in all animals within 48 hours after application.

The average score (24 to 72 hours) for irritation was calculated to be 0.0 for corneal opacity, iris and chemosis and 0.3 for conjunctival redness.

		Cornea		Iris	Conjunctiva
Animal	Reading	Opacity	Area involved		Redness	Chemosis	Discharge	Additional findings
1	1 hr	0	0	0	2	1	1
2	1 hr	0	0	0	1	0	0	Scleral vesseis injected, circumscribed area
3	1 hr	0	0	0	2	0	0	Scleral vesseis injected, circumscribed area
1	24 hrs	0	0	0	1	0	0
2	24 hrs	0	0	0	1	0	0	Scleral vesseis injected, circumscribed area
3	24 hrs	0	0	0	1	0	0
1	48 hrs	0	0	0	0	0	0
2	48 hrs	0	0	0	0	0	0
3	48 hrs	0	0	0	0	0	0
1	72 hrs	0	0	0	0	0	0
2	72 hrs	0	0	0	0	0	0
3	72 hrs	0	0	0	0	0	0
mean animal 1	24 - 72 hrs	0		0	0.3	0
mean animal 2	24 - 72 hrs	0		0	0.3	0
mean animal 3	24 - 72 hrs	0		0	0.3	0
mean 1 - 3	24/48/72 h	0.0		0.0	0.3	0.0

Interpretation of results:

GHS criteria not met

Conclusions:

Considering the described ocular reactions as well as the average score for irritation, the test article does not show an eye irritation potential under the test conditions chosen.

Executive summary:

The test article's potential to cause damage to the conjunctiva, iris or cornea was assessed by a single ocular application of 0.1 mL bulk volume (about 16 mg) of the test substance to one eye of three White New Zealand rabbits (stepwise procedure starting with one animal and supplementing two additional animals). The study was performed according to OECD test guideline 405 and in compliance with GLP. About 1 hour after application the eye was rinsed with tap water. The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application. Slight to moderate conjunctival redness, slight conjunctival chemosis and slight discharge were observed in the animals up to 24 hours after application. Two animals showed injected scleral vessels in a circumscribed area. The ocular reactions were reversible in all animals within 48 hours after application. The average score (24 to 72 hours) for irritation was calculated to be 0.0 for corneal opacity, iris and chemosis and 0.3 for conjunctival redness. In conclusion, considering the described ocular reactions as well as the average score for irritation, the test article is considered to be not irritating under the test conditions chosen.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

Irritation to skin was analyzed in a GLP-compliant study reliable without restrictions (BASF, 2005). The solid test substance was minimally moistened with a suitable amount of doubly-distilled water (corresponding to a dose of 0.5 g of unchanged test substance). The test substance was administered under semiocclusive conditions to the skin of 3 white A 1077 INRA (SPF) rabbits for 4 h to determine the irritant potential of the test substance. The mean score (24 - 48 -72 h) for erythema was 1. No edema was detected. All erythema were reversible within 7 days. The application area was slight black discolored in two animals during the observation period. Scaling was noticed in one animal at study termination, only. Based on the results of this study, the test substance was found to be not irritating to the rabbit skin.

 

Eye irritation

Irritation to eyes was analyzed in a GLP Guideline study (OECD 405) which was reliable without restrictions (BASF, 2005). Three white A 1077 INRA (SPF) rabbits received about 16 mg of the comminuted test substance (0.1 ml bulk volume). About 1 hour after application the eye was rinsed with tap water. The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application. Slight to moderate conjunctival redness, slight conjunctival chemosis and slight discharge were observed in the animais up to 24 hours after application. Two animais showed injected scleral vesseis in a circumscribed area. The ocular reactions were reversible in all animals within 48 hours after application. The average score (24 to 72 hours) for irritation was calculated to be 0.0 for corneal opacity, iris and chemosis and 0.3 for conjunctival redness. Considering the described ocular reactions as weil as the average score for irritation, the test substance did not show an eye irritation potential under the test conditions chosen.

 

Further toxicological data of category members:

Reliable data from several studies on irritation are available for the test article and for other members of the "perylene based pigments" category (see attached category justification). All of these data are taken into account for the evaluation and assessment of the irritation potential of the test article. Studies concerning the irritating potential for skin and eyes are available for all category members. In no study evidence for irritating or corrosive effects of the substances was observed. The category members can therefore all considered as not irritating to the skin and eyes.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. A GLP-compliant OECD 404 study is available for skin irritation. A GLP-compliant OECD 405 study is available for eye irritation. In both studies, the scores for the test item treated tissues were below the thresholds for classification as an irritant. As a result, the substance is not considered to be classified for skin or eye irritation under Regulation (EC) No. 1272/2008, as amended for the fourteenth time in Regulation (EC) No. 2020/217.