2,9-bis(p-methoxybenzyl)anthra[2,1,9-def:6,5,10-d'e'f']diisoquinoline-1,3,8,10(2H,9H)-tetrone

Endpoint summary

Description of key information

Skin irritation/corrosion: non-irritating, according to OECD TG 404, no GLP compliance, 0.5 ml of the test substance (50 % in water), occlusive, 4 h, rabbit, 1982, K2
Eye irritation: non-irritating, according to OECD TG 405, no GLP compliance, 0.1 ml of the test substance, no washing, rabbit, 1982, K2

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

only a 50% aqueous preparation was tested

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gaukler; D-6050 Offenbach/Main, FRG
- Housing: Stainless steel with wire mesh walk floor, floor area: 40 cm x 51 cm
- Diet (e.g. ad libitum): Ovator Solikanin 4 mm; Muskator-Werke, D-4000 Düsseldorf 1, FRG (about 130 g per animal daily)
- Water (e.g. ad libitum): 250 ml tap water per animal daily
- Acclimation period: At least approx. 8 days in the skin laboratory before the beginning of the study; same housing conditions as during the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): fully airconditioned rooms
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

other: untreated skin of the same animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): 50% aqueous preparation
Application volume: Wetting of the test patch with a layer of approx. 0.5 ml of the 50% preparation (the test patch measures 2.5 x 2.5 cm and thus about 0.5 g is applied; due to the natural moisture of the skin, distilled water is used for preparing the preparations in order to carry out the test under conditions am physiological as possible.

Duration of treatment / exposure:

4 hours

Observation period:

30 - 60 minutes after removal of the test patches and 24 hours, 48 hours, 72 hours and 8 days after the beginning of application

Number of animals:

2 females, 1 male

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with Lutrol and Lutrol/water (1:1)
- Time after start of exposure: 4 h

SCORING SYSTEM: Scale for scoring of erythema and edema:
0 = None
1 = Very slight
2 = Well-defined
3 = Moderate to severe
4 = Severe to very severe

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 4 h

Score:

2

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.9

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 4 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

After 4 hours, erythema score 2 (extending beyond the area of exposure) was observed in all animals; edema score 1 was observed in one animal; edema extending beyond the area of exposure in one animal.
After 24 hours, erythema extending beyond the area of exposure (score 1 in two animals and score 2 in one animal). In two animals, the erythema persisted at score 1 until the 72 h time point. reversibvle within 8 days.

Other effects:

No abnormalities identified at necropsy.

Overview on results:

		Animal 1	Animal 2	Animal 3
erythema	4 h	2	2	2
	24 h	2	1	1
	48 h	1	1	0
	72 h	1	1	0
	8 d	0	0	0
edema	4 h	0	0	1
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0
	8 d	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of this study, the test article caused a mild irritation response below the level of regulatory significance and is therefore considered to be not irritating to the rabbit skin.

Executive summary:

In a skin irritation study following OECD guideline 404, 500 mg of a 50% aequous preparation of the test substance was applied to the left flanks of three Vienna White rabbits. The untreated right flan served as control. The animals were observed for 8 days. An edema extending beyond the area of exposure with a score of 1 was observed in one animal after 4 hours, reversible within 24 hours. In addition, erythema formation (score = 2) was observed in all animals 4 hours after exposure. The erythema extended beyond the area of exposure in all animals at this observation time point. The severity of erythema decreased during the observation period and was fully reversible in all animals within 8 days. The mean (24/48/72 h) erythema and edema scores were 0.9 and 0, respectively. Based on the results of this study, the test article caused a mild irritation response below the level of regulatory significance and is therefore considered to be not irritating to the rabbit skin.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Gaukler; D-6050 Offenbach/Main, FRG
- Weight at study initiation: 2.79, 2,89 and 2.93 kg (individual weights)
- Housing: Stainless steel with wire mesh walk floor, floor area: 40 cm x 51 cm
- Diet (e.g. ad libitum): Ovator Solikanin 4 mm; Muskator-Werke D-4000 Düsseldorf 1, FRG (about 130 g per animal daily)
- Water (e.g. ad libitum): About 250 ml tap water per animal, daily
- Acclimation period: At least approx. 8 days in the skin laboratory before the beginning of the study; same housing conditions as during the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 -24
- Humidity (%): 30 - 70
- Air changes (per hr): Fully airconditioned room
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (ca. 28 mg)

Duration of treatment / exposure:

one single application, no washing was performed

Observation period (in vivo):

1 h, 24 h, 48 h, 72 h, 8 d after application

Number of animals or in vitro replicates:

2 females, 1male

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 1 h

Score:

2

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

not fully reversible within: 8 days (one animal had a conjunctivae score of 1 after 8 days)

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 1 h

Score:

1

Max. score:

4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

The ocular reactions observed were below the regulatory threshold. The remaining redness at the end of observation in one animal is expected to resolve eventually.

Overview of results:

		Animal 1	Animal 2	Animal 3
cornea	1 h	0	0	0
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0
	8 d	0	0	0
redness	1 h	2	2	2
	24 h	2	2	2
	48 h	1	1	1
	72 h	1	1	1
	8 d	1	0	0
chemosis	1 h	1	1	1
	24 h	1	1	1
	48 h	0	0	0
	72 h	0	0	0
	8 d	0	0	0
Iris	1 h	0	0	0
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0
	8 d	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of this study, the test article caused mild ocular reactions below the level of significance and is therefore regarded as not irritating to the rabbit eye.

Executive summary:

In an eye irritation study following OECD guideline 405, 0.1 ml of the test substance was applied undiluted into the eyes of three Vienna White rabbits. The test animals were observed for eight days and irritation scores were recorded 1, 24, 48 and 72 hours and 8 days after the instillation. No effects in the cornea and iris were observed at any observation time point. The mean scores (24, 48, 72 hours) for conjunctival redness and chemosis were 1.3 and 0.3, respectively. One animal displayed a conjunctival redness of at the end of the observation period with a score of 1 (full reversibility is expected after longer observation). Chemosis was fully reversible within 48 hours. Based on the results of this study, the test article caused mild ocular reactions below the level of significance and is therefore regarded as not irritating to the rabbit eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

In a skin irritation study following OECD guideline 404, 500 mg of a 50% aequous preparation of the test substance was applied to the left flanks of three Vienna White rabbits (BASF AG, 1982). The untreated right flan served as control. The animals were observed for 8 days. An edema extending beyond the area of exposure with a score of 1 was observed in one animal after 4 hours, reversible within 24 hours. In addition, erythema formation (score = 2) was observed in all animals 4 hours after exposure. The erythema extended beyond the area of exposure in all animals at this observation time point. The severity of erythema decreased during the observation period and was fully reversible in all animals within 8 days. The mean (24/48/72 h) erythema and edema scores were 0.9 and 0, respectively. Based on the results of this study, the test article caused a mild irritation response below the level of regulatory significance and is therefore considered to be not irritating to the rabbit skin.

 

Eye irritation

In an eye irritation study following OECD guideline 405, 0.1 ml of the test substance was applied undiluted into the eyes of three Vienna White rabbits (BASF AG, 1982). The test animals were observed for eight days and irritation scores were recorded 1, 24, 48 and 72 hours and 8 days after the instillation. No effects in the cornea and iris were observed at any observation time point. The mean scores (24, 48, 72 hours) for conjunctival redness and chemosis were 1.3 and 0.3, respectively. One animal displayed a conjunctival redness of at the end of the observation period with a score of 1 (full reversibility is expected after longer observation). Chemosis was fully reversible within 48 hours. Based on the results of this study, the test article caused mild ocular reactions below the level of significance and is therefore regarded as not irritating to the rabbit eye.

 

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. An OECD 404 study is available for skin irritation. An 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.