4,11-dichloro-5,12-dihydroquino[2,3-b]acridine-7,14-dione

Endpoint summary

Description of key information

Skin irritation/corrosion: Read-across, non-irritating

Eye irritation: Read-across, non-irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Please see the attached justification.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Remarks on result:

no indication of irritation

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:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Please see the attached justification.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Remarks on result:

no indication of irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

 

4, 11 -Dichloroquinacridone has not been tested for skin irritation. However, mortality, clinical signs, changes in body weights or toxicological relevant changes in necropsy were not observed in acute dermal toxicity studies with other quinacridone pigments (Pigment Violet 19 and Pigments Red 122 and 282). Therefore, the members of the quinacridone pigments category are not classified for acute dermal toxicity. In addition, several reliable data on skin irritation are available for the quinacridone pigments (Pigment Violet 19 and Pigments Red 122, 202, 209 and 282).

 

In a reliable study according to FDA guideline (Klimisch score 2), Pigment Violet 19 was administered to six Himalayan albino rabbits. Both intact and scarified skin sites were exposed to 500 mg test substance (pasted in 0.7 mL PEG 400) for 24 h under occlusive conditions and the skin responses were watched for up to 72 hours. No skin reactions were observed.

 

In a reliable GLP-conform study according to OECD TG 404 (Klimisch score 1), Pigment Red 122 was administered to three New Zealand White rabbits. Shaved, intact skin of the left flank was exposed to 500 mg test substance for 4 hours under semi-occlusive conditions. The scoring of skin reactions was performed 1, 24, 48 and 72 hours, as well as 7, 10 and 14 days after removal of the dressing. The mean erythema/eschar score of the three animals was 0.00, 0.33 and 0.00, respectively and the mean oedema score was 0.00 for all three animals.

 

In a reliable GLP-conform study according to EPA guideline (Klimisch score 1), Pigment Red 202 was administered to six New Zealand White rabbits. Clipped, intact skin was exposed to 500 mg test substance for 4 hours under semi-occlusive conditions and the skin responses were watched for up to 72 hours. Besides the purple staining of the dose site, no relevant skin reactions were observed.

In a reliable study according to FDA guideline (Klimisch score 2), the Pigment Red 209 was administered to six Himalayan albino rabbits. Both intact and scarified skin sites were exposed to 500 mg test substance (pasted in 0.5 mL PEG 400) for 24 h under occlusive conditions and the skin responses were watched for up to 72 hours. No skin reactions were observed.

 

In a reliable GLP-conform study according to OECD TG 404 (Klimisch score 1), Pigment Red 282 was administered to three New Zealand White rabbits (one male, two female). Clipped, intact skin was exposed to 500 mg test substance for 4 hours under semi-occlusive conditions. Besides the purple staining of the dose site, no relevant skin reactions were observed.

 

Several supporting studies and secondary sources from literature confirm these findings. Additionally, the absence of a local irritation potential has been consistently observed for organic pigments in general (Stratmann et al, 2020). The insolubility in physiological fluids impedes a potential for irritation.

 

Therefore, no classification for skin irritation is necessary for the members of the Quinacridone Pigments category.

 

Eye irritation

 

4, 11 -Dichloroquinacridone has not been tested for eye irritation, but several reliable data are available for other quinacridone pigments (Pigment Violet 19 and Pigments Red 122, 202, 209 and 282).

 

In a reliable GLP-conform study according to OECD TG 405 (Klimisch score 1), 100 mg of Pigment Violet 19 was administered to the eyes of three New Zealand White rabbits. Within the 72-hour observation period no corneal or iridial effects were observed. Chemosis was not found likewise. Conjunctival redness was observed in all animals at one hour after instillation as well as in 2/3 animals at the 24 h reading. This effect was fully reversible by 48 hours after application.

 

In a reliable GLP-conform study according to OECD TG 405 (Klimisch score 1), 100 mg of Pigment Red 122 was administered to the eyes of three New Zealand White rabbits. Within the 72-hour observation period no corneal or iridial effects were observed. One and 24 hours after treatment the conjunctivae of the animals showed definitely injected blood vessels up to a diffuse crimson red colour. Additionally, a very slight swelling and slight from substance coloured eye discharge were observed in one animal one hour after treatment. These effects were fully reversible by 48 hours after application.

In a reliable GLP-conform study according to EPA guideline (Klimisch score 1), 100 mg of the Pigment Red 202 was administered to six New Zealand White rabbits. Within the 72-hour observation period no corneal or iridial effects were observed. Chemosis was not found likewise. Conjunctival redness was observed in 1/6 animals at 24 hours after instillation. This effect was fully reversible by 48 hours after application.

 

In a reliable study according to FDA guideline (Klimisch score 2), 100 mg of Pigment Red 209 (pasted with 3 drops of PEG 400) was administered to six Himalayan rabbits. Within the 72-hour observation period no corneal or iridial effects were observed. Conjunctival redness was observed in all animals at one and seven hours after instillation, as well as in 5/6 animals at the 24 h reading. These effects were fully reversible by 72 hours after application in 5/6 animals. In one animal this score ameliorated from 1 to 0 at the 48-hour reading, but then increased again to 1 at the 72-hour reading. Chemosis was visible in 2/6 animals at the one hour reading and still in 1/6 animals at the 7-hour and 24-hour reading. This effect was fully reversible by 48 hours after application.

 

In a reliable GLP-conform study according to OECD TG 405 (Klimisch score 1), 100 mg of Pigment Red 282 was administered to three New Zealand White rabbits. Within the 72-hour observation period no corneal or iridial effects were observed. Chemosis was not found likewise. Slight conjunctival redness was observed in 2/3 animals at one hour after instillation and persisted up to the 24-hour examination in one of these animals. Slight reddening of the sclerae was present in all animals at the 1-hour reading. In one animal there was a slight ocular discharge noted at the same time. These findings were reversible within 48 hours.

 

Several supporting studies and secondary sources from literature confirm these findings. Additionally, the absence of a local irritation potential has been consistently observed for organic pigments in general (Stratmann et al, 2020). The insolubility in physiological fluids impedes a potential for irritation.

 

Therefore, no classification for eye irritation is necessary for the members of the Quinacridone Pigments category.

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. Several in-vivo studies with related quinacridone pigments are available for skin and eye irritation. The scores for the test item treated tissues were consistently 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 17th time in Regulation (EC) No. 2021/849.