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

Endpoint summary

Description of key information

Oral: Read-across, LD50 > 2000 mg/kg bw

Inhalation: Read-across, LC50 > 3.1 mg/L

Dermal: no data availabe

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality and no clinical signs were observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

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

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 mg/L air

Based on:

test mat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

3.1 mg/L air

Physical form:

inhalation: dust

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and, in the absence of an in vivo study by the oral route, no systemic effects after dermal exposure are predicted on the basis of non-testing approaches (e.g. read across, QSAR studies)

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute toxicity: oral

 

4, 11 -Dichloroquinacridone has not been tested for acute oral toxicity. However, it did not cause mortality, clinical signs, changes in hematology or in organ weights upon 14 -day gavage-dosing in rats with 1000 mg/kg bw. In addition, no mortality or toxicological relevant changes in necropsy were observed in reliable acute oral toxicity studies with other quinacridone pigments (Pigment Violet 19_CAS1047-16-1 and Pigments Red 122_CAS980-26-7, 202_CAS3089-17-6, 209_CAS38720-66-0 and 282_CAS938065-79-3).

 

In a reliable non-GLP study similar to OECD TG 401 (Klimisch score 2), Pigment Violet 19 was administered in starch mucilage to ten female Wistar rats at a limit dose of 10000 mg/kg bw by gavage. During the 14 days observation period no animals died and there were no toxicological relevant changes found in necropsy, thus leading to a median lethal dose (LD50) > 10000 mg/kg bw.

In a reliable GLP-conform study according to OECD TG 423 (Klimisch score 1), Pigment Red 122 was administered in PEG 300 to two groups, each of three female HanRcc:WIST (SPF) rats at a limit dose of 2000 mg/kg bw by gavage. During the 14 days observation period no animals died and there were no toxicological relevant changes found in necropsy, thus leading to a median lethal dose (LD50) > 2000 mg/kg bw.

In a reliable GLP-conform study according to EPA guideline (Klimisch score 1), Pigment Red 202 was administered in corn oil to ten Wistar rats (five per sex) at a limit dose of 5000 mg/kg bw by gavage. During the 14 days observation period no animals died and there were no toxicological relevant changes found in necropsy, thus leading to a median lethal dose (LD50) > 5000 mg/kg bw.

In a reliable non-GLP study similar to OECD TG 401 (Klimisch score 2), Pigment Red 209 was administered in sesame oil to ten female Hoe WISKf (SPF71) rats at a limit dose of 10000 mg/kg bw by gavage. During the 14 days observation period no animals died and there were no toxicological relevant changes found in necropsy, thus leading to a median lethal dose (LD50) > 10000 mg/kg bw.

In a reliable GLP-conform study according to OECD TG 423 (Klimisch score 1), Pigment Red 282 was administered in corn oil to two groups, each of three female HanBrl: Wist (SPF) rats at a limit dose of 2000 mg/kg bw by gavage. During the 14 days observation period no animals died and there were no toxicological relevant changes found in necropsy, thus leading to a median lethal dose (LD50) > 2000 mg/kg bw.

 

Several supporting studies and secondary sources from literature confirm these findings. Even in tests performed with much higher concentrations in the range of 5000 to 15000 mg/kg bw no animals died during the post observation period.

 

Therefore, no classification for acute oral toxicity is necessary for the members of the Quinacridone Pigments category.

 

Acute toxicity: inhalation

 

4, 11 -Dichloroquinacridone has not been tested for acute inhalation toxicity, but a short-term inhalation study (similar to OECD TG 412, but instead of 28 only 5 days) is ongoing. However, several reliable data are available for other quinacridone pigments (Pigment Violet 19_CAS1047-16-1 and Pigments Red 122_CAS980-26-7).

 

In a reliable study (Klimisch score 2), male rats have been exposed to 3.1 mg/L of Pigment Violet 19 for 4 h. The test atmosphere contained only about 21% particles with an aerodynamic diameter (corresponding to 0.651 mg test item of respirable size). All animals survived the 14 day observation period, resulting in a LC50 value of > 3.1 mg/L (corresponding to 0.651 mg/L respirable test item) for the inhalation of dust.

 

In a reliable GLP-conform study according to OECD TG 403 (Klimisch score 1) rats were exposed to the maximum technically feasible aerosol concentration of 3.1 mg/L (MMAD about 2.7 μm) of Pigment Red 122. No lethal effects, no severe clinical symptoms indicating a life-threatening or moribund state, and no gross morphological abnormalities were observed.

 

Therefore, no classification for acute inhalation toxicity is necessary for the members of the Quinacridone Pigments category.

 

Acute toxicity: dermal

 

4, 11 -Dichloroquinacridone has not been tested for acute dermal toxicity. However, the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and, in the absence of an in vivo study by the oral route, no systemic effects after dermal exposure are predicted on the basis of non-testing approaches (e.g. read across). Furthermore, several reliable data are available for other quinacridone pigments (Pigment Violet 19_CAS1047-16-1 and Pigments Red 122_CAS980-26-7 and 282_CAS938065-79-3).

 

In one acute dermal toxicity study (Klimisch score 3), Pigment Violet 19 was administered to the intact or abraded rabbit skin (3 animals for each condition) at a dose of 2 mL/kg bw. No animal died within the 14-days observation period, resulting in a LD50 > 2 mL/kg bw. This study was judged not to be reliable, because relevant information (e.g., test item purity, duration of exposure) are missing. Nevertheless, these data support the results obtained with other members of this category, which did not show acute dermal toxicity, too.

 

In another acute dermal toxicity study (secondary literature, Klimisch score 4), Pigment Red 122 was administered at a dose of 3000 mg/kg (in the form of an aqueous slurry) to the shaved, abraded skin of the backs of 4 New Zealand White rabbits. No animal died within the observation period, resulting in a LD50 > 3000mg/kg bw.

 

In a reliable GLP-conform study according to OECD TG 402 (Klimisch score 1), Pigment Red 282 was administered as a suspension in corn oil on the skin of ten rats (HanBrl : Wist) at the limit dose of 2000 mg/kg bw. No animal died within the observation period, resulting in a LD50 > 2000mg/kg bw.

 

Therefore, no classification for acute dermal toxicity 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. No mortality occurred at the limit dose of 2000 mg/kg bw with related quinacridone pigments. The substance itself caused no clinical signs and adverse findings in a 14 -day gavage study with 1000 mg/kg bw.  As a result, the substance is not considered to be classified for acute oral or dermal toxicity under Regulation (EC) No. 1272/2008, as amended for the 17th time in Regulation (EC) No. 2021/849.