2,9-dimethylanthra[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, similar to OECD TG 404, non-GLP, 0.5 g test substance, rabbit, 1983, K1
Eye irritation: non-irritating, similar to OECD TG 405, non-GLP, 0.1 g test substance in 0.01 ml PEG, rabbit, 1978, 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:

July 5th, 1983 - July 8th, 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Remarks:

but QAU statement included

Specific details on test material used for the study:

- Physical state: solid (powder)
- technical grade
- Storage condition of test material: in the dark at room temperature

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HOECHST AG, Kastengrund
- Weight at study initiation: 2.7 - 3.2 kg
- Housing: individually
- Diet (e.g. ad libitum): Altromin 2013 breeding diet - rabbit (Altromin GmbH, Lage/Lippe), ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): fully conditioned room
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: polyethylenglycol 400

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg in 0.3 mL polyethylenglycol 400

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: cellulose gauze held in place with an adhesive plaster (Fa. Baiersdorf AG, Hamburg)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 4 hours

SCORING SYSTEM: According to OECD guidelines

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.2

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

0.5 - 1 hour after treatment, erythema score 1 was observed in 1/3 animals and edema score 1 was observed in 3/3 animals.
The treated skin was red colored from the test substance.
At 72 hours after treatment two animals showed a dry and rough skin.

Overview of Results:

		Animal 1	Animal 2	Animal 3
erythema	1 h	0	1	0
	24 h	1	0	0
	48 h	0	0	1
	72 h	0	0	0
edema	1 h	1	1	1
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance was investigated for its potential to irritate the skin. Under the conditions chosen, the test substance was concluded to be not irritating.

Executive summary:

In the study 0.5 g of the test substance in 0.3 ml PEG 400 was applied to the skin of three New Zealand White rabbits in a study according to OECD guideline 404. The animals were observed for 72 hours. 0.5 - 1 hour after treatment, erythema score 1 was observed in 1/3 animals and edema score 1 was observed in 3/3 animals. The mean scores (24, 48 and 72 hours) for erythema and edema were 0.2 and 0, respectively. The treated skin was red coloured from the test substance. At 72 hours after treatment two animals showed a dry and rough skin. Based on the results of this study, the test article was considered to be not irritating to the 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

Study period:

July 5th, 1983 - July 8th, 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Remarks:

but QAU statement included

Specific details on test material used for the study:

- Physical state: solid (powder)
- technical grade
- Storage condition of test material: in the dark at room temperature

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: HOECHST AG breed
- Weight at study initiation: 3.5 - 3.9 kg
- Housing: individually
- Diet (e.g. ad libitum): Altromin 2013 breedingdiat - rabbit (Altromin GmbH, Lage/Lippe), ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): fully conditioned room
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:

other: polyethylenglycol 400

Controls:

other: untreated eye of the same animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg in 0.01 mL polyethylenglycol 400

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with physiological NaCl solution of 37 °C (0.01%)
- Time after start of exposure: 24 hours

SCORING SYSTEM: According to OECD test guideline

TOOL USED TO ASSESS SCORE: magnifier, fluorescein solution (0.01%) and UV light

Irritation parameter:

other: fluorescent test

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: after 1 h of exposure the iris was brownish colored in two of the animals

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No signs of irritation were observed for the iris and the cornea at 24-72h timepoints. After 1 h of exposure the iris was brownish colored in two of the animals. A moderate (grade 1) redness and swelling of the conjunctival sac was observed after 1 h of exposure which both decreased gradually. No swelling was observed from 24 hours onwards and no redness was observed at 72 hours.

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
redness	1 h	1	1	1
	24 h	1	1	0
	48 h	1	0	0
	72 h	0	0	0
chemosis	1 h	1	0	1
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0
Iris	1 h	0	0	0
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance was investigated for its potential to be irritant to eyes. All effects observed were fully reversible within 72 h and thus, it was concluded that the test substance is not irritating to eyes.

Executive summary:

In the key study according to OECD guideline 405, the test article (0.1 g in 0.01 ml polyethylenglycol 400) was applied into the left conjunctival sac of three New Zealand White rabbits. The untreated right eyes served as controls. The treated eyes were washed with physiological NaCl solution 24 hours after instillation. Animals were observed 1, 24, 48 and 72 hours after test item instillation. After 1 h of exposure the iris was brownish colored in two of the animals. A moderate (grade 1) redness and swelling of the conjunctival sac was observed after 1 h of exposure which both decreased gradually. No swelling was observed from 24 hours onwards and no redness was observed at 72 hours. The mean (24, 48, 72 hours) cornea, iris and chemosis scores were 0. The mean (24, 48, 72 hours) conjunctivae score was 0.3 (fully reversible within 72 hours). Based on the result of this study, the test article was considered to be not irritating to the 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 the key study (Hoechst, 1983) 0.5 g of the test substance in 0.3 ml PEG 400 was applied to the skin of three New Zealand White rabbits in a study according to OECD guideline 404. The animals were observed for 72 hours. 0.5 - 1 hour after treatment, erythema score 1 was observed in 1/3 animals and edema score 1 was observed in 3/3 animals. The mean scores (24, 48 and 72 hours) for erythema and edema were 0.2 and 0, respectively. The treated skin was red coloured from the test substance. At 72 hours after treatment two animals showed a dry and rough skin. Based on the results of this study, the test article was considered to be not irritating to the skin.

 

Supporting information:

In one supporting study performed according to the Code of Federal Regulations Title 16, the test substance (0.5 g) was applied to the skin of six New Zealand White rabbits (Hazleton Laboratories Europe Ltd., 1978). The treatment duration was 24 hours (under occlusive conditions) and the animals were observed for 7 days thereafter. The mean (24 and 72 hours) scores for erythema and edema were 0. Based on the results of this study, the test article was considered to be not irritating to the skin.

In another supporting non-GLP study according to a method comparable to OECD guideline 404, the test substance was applied as moistened powder (50% in water) for 20 hours to the back of two rabbits (BASF, XXIV/269, 1976). Remaining colored test substance was observed at 24 hours and erythema could not be scored. No erythema was reported 8 days after treatment. No edema was reported at 24 hours and 8 days.

In the third supporting non-GLP study according to a method comparable to OECD guideline 404, a mixture containing 18.5% of the test substance was applied for 20 hours to the back of two rabbits (BASF, XXIV/334, 1976). Remaining colored test substance was observed at both observation time points (24 hours and 8 days) and therefore erythema could not be scored. No edema was reported at the 24 hours and 8 days observation time points.

 

Eye irritation

In the key study according to OECD guideline 405, the test article (0.1 g in 0.01 ml polyethylenglycol 400) was applied into the left conjunctival sac of three New Zealand White rabbits (Hoechst AG, 1983). The untreated right eyes served as controls. The treated eyes were washed with physiological NaCl solution 24 hours after instillation. Animals were observed 1, 24, 48 and 72 hours after test item instillation. After 1 h of exposure the iris was brownish colored in two of the animals. A moderate (grade 1) redness and swelling of the conjunctival sac was observed after 1 h of exposure which both decreased gradually. No swelling was observed from 24 hours onwards and no redness was observed at 72 hours. The mean (24, 48, 72 hours) cornea, iris and chemosis scores were 0. The mean (24, 48, 72 hours) conjunctivae score was 0.3 (fully reversible within 72 hours). Based on the result of this study, the test article was considered to be not irritating to the eye.

 

Supporting information:

In a supporting study performed according to the Code of Federal Regulations Title 16, the test substance (0.1 g) was instilled into the eyes of six New Zealand White rabbits (Hazleton Laboratories Europe Ltd., 1978). The treated eyes were not washed. The mean (24, 48, 72 hours) cornea, iris and chemosis scores were 0. The mean (24, 48, 72 hours) conjunctivae score was 0.056 (fully reversible within 48 hours). Therefore, the test article was considered to be not irritating.

In another supporting study performed with two rabbits, 50 µl of the test article was applied into the conjunctival sac of the right eyes (BASF, XXIV/269, 1976). The left eyes was treated with talcum powder and served as controls. The eyes were not rinsed. Animals were observed after 1 and 24 hours and after 8 days after the treatment. After 1 hour, remaining substance was observed. The application caused slight redness of the conjunctivae at 1 and 24 hours. Redness was fully reversible within 8 days. One animal displayed a minimal corneal reaction at the end of the observation perio. The irritation observed caused by the test article was not clearly different from the control substance talcum powder. The test article was therefore judged to be not irritating to the eyes.

In the third supporting study (BASF, XXIV/334, 1976), 50 µl of a mixture containing 18.5% of the test article was instilled into conjunctival sac of the right eyes of two rabbits. Physiological sodium chloride solution (50 µl) was instilled into the left eyes and served as controls. The eyes were not rinsed. Animals were observed after 1 and 24 hours and after 8 days after the treatment. After 1 hour, remaining substance was observed. The application did not cause any irritating effects. One animal displayed a minimal corneal reaction at the end of the observation period. This reaction was however also observed with the control substance, therefore the test article was considered to be not irritating.

 

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 non-GLP study according to OECD 404 is available for skin irritation. A non-GLP study according to OECD 405 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.