1,4-bis[(4-butylphenyl)amino]-5,8-dihydroxyanthraquinone

Endpoint summary

Description of key information

The skin sensitization potential of 1,4-Bis(4-butylanilino)-5,8-dihydroxyanthraquinone (CAS no. 28198 -05 -2) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. The substance 1,4-Bis(4-butylanilino)-5,8-dihydroxyanthraquinone was predicted to be non sensitizing to the skin of female CBA/Ca mice.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation

Remarks:

in vivo

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

data is from OECD QSAR toolbox v3.3 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Type of study:

mouse local lymph node assay (LLNA)

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

- Name of test material: 1,4-Bis(4-butylanilino)-5,8-dihydroxyanthraquinone
- Molecular formula: C34H34N2O4
- Molecular weight: 534.6526 g/mole
- Smiles notation: CCCCc1ccc(cc1)Nc2ccc(c3c2C(=O)c4c(ccc(c4C3=O)O)O)Nc5ccc(cc5)CCCC
-InChl:1S/C34H34N2O4/c1-3-5-7-21-9-13-23(14-10-21)35-25-17-18-26(36-24-15-11-22(12-16-24)8-6-4-2)30-29(25)33(39)31-27(37)19-20-28(38)32(31)34(30)40/h9-20,35-38H,3-8H2,1-2H3
- Substance type: Organic
- Physical state: Solid

Species:

mouse

Strain:

CBA/Ca

Sex:

female

Details on test animals and environmental conditions:

no data available

Vehicle:

unchanged (no vehicle)

Concentration:

0-25%

No. of animals per dose:

4

Details on study design:

no data available

Positive control substance(s):

not specified

Statistics:

no data available

Positive control results:

no data available

Other effects / acceptance of results:

no data available

Parameter:

SI

Test group / Remarks:

test group

Remarks on result:

no indication of skin sensitisation based on QSAR/QSPR prediction

Cellular proliferation data / Observations:

no data available

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

((((((("a" or "b" or "c" or "d" )  and "e" )  and ("f" and ( not "g") )  )  and "h" )  and "i" )  and "j" )  and ("k" and "l" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Hydroquinones OR Phenols, Poly by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkyl arenes OR Anthracenone/ Antracendione OR Aromatic amine OR Aryl OR Cycloketone OR Diketone OR Fused carbocyclic aromatic OR Phenol by Organic Functional groups ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkyl arenes OR Anthracenone/ Antracendione OR Aromatic amine OR Aryl OR Overlapping groups OR Phenol by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] OR Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aliphatic Nitrogen, two aromatic attach [-N-] OR Aromatic Carbon [C] OR Carbonyl, olefinic attach [-C(=O)-] OR Diarylketone OR Hydroxy, aromatic attach [-OH] OR Ketone in a ring, olefinic aromatic attach OR Miscellaneous sulfide (=S) or oxide (=O) OR Nitrogen, two or tree olefinic attach [>N-] OR Olefinic carbon [=CH- or =C<] OR Ortho-hydroxy to misc. -CO-  OR Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3 ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) OR Highly reactive (GSH) >> Furamates (MA) by Protein binding potency

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Alkyl arenes AND Anthracenone/ Antracendione AND Aromatic amine AND Aryl AND Overlapping groups AND Phenol by Organic Functional groups (nested) ONLY

Domain logical expression index: "j"

Similarity boundary:Target: CCCCc1ccc(Nc2ccc(Nc3ccc(CCCC)cc3)c3c2C(=O)c2c(O)ccc(O)c2C3=O)cc1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is >= 9.09

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is <= 13.9

Interpretation of results:

other: not sensitizing

Conclusions:

1,4-Bis(4-butylanilino)-5,8-dihydroxyanthraquinone was predicted to be non sensitizing to the skin of female CBA/Ca mice.

Executive summary:

The skin sensitization potential of 1,4-Bis(4-butylanilino)-5,8-dihydroxyanthraquinone was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. 1,4-Bis(4-butylanilino)-5,8-dihydroxyanthraquinone was predicted to be non sensitizing to the skin of female CBA/Ca mice.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization:

Various studies has been investigated for the test chemical1,4-bis[(4-butylphenyl)amino]-5,8-dihydroxy-9,10-dihydroanthracene-9,10-dione (CAS no. 28198 -05 -2)to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs for target chemical1,4-bis[(4-butylphenyl)amino]-5,8-dihydroxy-9,10-dihydroanthracene-9,10-dione (CAS no. 28198 -05 -2) and its structurally similar read across substances4,4'-Methylenebis(2,6-di-tert-butylphenol)(CAS no: 118-82-1) and 4-octyl-N-(4-octylphenyl)aniline (CAS no: 101-67-7).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

The skin sensitization potential of 1,4-Bis(4-butylanilino)-5,8-dihydroxyanthraquinone was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. 1,4-Bis(4-butylanilino)-5,8-dihydroxyanthraquinone was predicted to be non sensitizing to the skin of female CBA/Ca mice.

 

The MAK Collection for Occupational Health and Safety (2014) conducted a maximization test of Magnusson and Kligman for structurally similar read across substance4,4'-Methylenebis(2,6-di-tert-butylphenol)(CAS no: 118-82-1) on ten male and female Dunkin-Hartley guinea pigs. Intradermal Induction was carried out with 0.5% of 4,4'-methylenebis (2,6-di-tert-butylphenol), and Freund's adjuvant and the epidermal induction was performed one week later at 50% of 4 , 4'-methylenebis (2,6-di-tert-butylphenol) in vaseline. After the non treatment period of 2 weeks, animals were challenged at the same concentration used during epidermal induction (50% in vaseline). None of the treated guinea pigs showed positive response at 24, 48 or 72 hours. Therefore the chemical 4,4'-Methylenebis(2,6-di-tert-butylphenol)(CAS no: 118-82-1) was considered to be not sensitizing onDunkin-Hartley guineapigs’ skin.

 

The above results were supported by modified Landsteiner testperformed bythe MAK Collection for Occupational Health and Safety (2012)forstructurally similar read across substance4-octyl-N-(4-octylphenyl)aniline (CAS no: 101-67-7) on guinea pigs’ skin . Negative skin effects were observed when the guinea pigs were exposed to the chemical 4-octyl-N-(4-octylphenyl)aniline. Hence under the test condition, the chemical 4-octyl-N-(4-octylphenyl)aniline (CAS no: 101-67-7) was considered to be not sensitizing on skin of guinea pigs.

 

Based on the available data for the target and read across substances and applying the weight of evidence approach,it can be concluded thatchemical 1,4-bis[(4-butylphenyl)amino]-5,8-dihydroxy-9,10-dihydroanthracene-9,10-dione (CAS no. 28198 -05 -2) is unable to cause contact sensitization and considered as not sensitizing .Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance 1,4-bis[(4-butylphenyl)amino]-5,8-dihydroxy-9,10-dihydroanthracene-9,10-dione (CAS no. 28198 -05 -2) and its structurally similar read across substances 4,4'-Methylenebis(2,6-di-tert-butylphenol)(CAS no: 118-82-1) and 4-octyl-N-(4-octylphenyl)aniline (CAS no: 101-67-7) were observed in various studies. From the results obtained from these studies it is concluded that the chemical 1,4-bis[(4-butylphenyl)amino]-5,8-dihydroxy-9,10-dihydroanthracene-9,10-dione (CAS no. 28198 -05 -2) is not likely to cause skin sensitization and hence can be classified as non skin sensitizer.