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

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

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 version 3.3 and the supporting QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.3, 2017

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

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

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Details on mammalian cell type (if applicable):

Not applicable.

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

not specified

Metabolic activation:

with

Metabolic activation system:

S9 Metabolic activation

Test concentrations with justification for top dose:

not specified

Vehicle / solvent:

not specified

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Details on test system and experimental conditions:

not specified

Rationale for test conditions:

not specified

Evaluation criteria:

Prediction was done considering a dose dependent increase in the number of revertants/plate.

Statistics:

not specified

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

Not specified.

Remarks on result:

other: No mutagenic effect were observed

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
Estimation method: Takes highest mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

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 Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, non cyclic structure OR Non binder, without OH or NH2 group OR Strong binder, NH2 group OR Strong binder, OH group OR Very strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is >= 7.19

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is <= 17.7

Conclusions:

1,4-bis[(4-butylphenyl)amino]-5,8-dihydroxy-9,10-dihydroanthracene-9,10-dione (28198-05-2) was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 1,4-bis[(4-butylphenyl)amino]-5,8-dihydroxy-9,10-dihydroanthracene-9,10-dione (28198-05-2). The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with S9 metabolic activation system. 1,4-bis[(4-butylphenyl)amino]-5,8-dihydroxy-9,10-dihydroanthracene-9,10-dione was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 1,4-bis[(4-butylphenyl)amino]-5,8-dihydroxy-9,10-dihydroanthracene-9,10-dione (28198-05-2). The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without S9 metabolic activation system. 1,4-bis[(4-butylphenyl)amino]-5,8-dihydroxy-9,10-dihydroanthracene-9,10-dione was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence and absence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Genetic toxicity in vitro;

Prediction model based estimation and data from read across chemical have been reviewed to determine the mutagenic nature of 1,4-bis[(4-butylphenyl)amino]-5,8-dihydroxy-9,10-dihydroanthracene-9,10-dione (28198-05-2) . The studies are as mentioned below

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 1,4-bis[(4-butylphenyl)amino]-5,8-dihydroxy-9,10-dihydroanthracene-9,10-dione (28198-05-2). The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without S9 metabolic activation system. 1,4-bis[(4-butylphenyl)amino]-5,8-dihydroxy-9,10-dihydroanthracene-9,10-dione was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence and absence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

In a study for structurally and functionally similar read across chemical, Gene mutation toxicity study was performed by Joseph P. Brownet al. (Mutation Research,1978) to determine the mutagenic nature of Sudan VI IUPAC : 1-({2-methyl-4-[(2-methylphenyl)diazenyl]phenyl}diazenyl)-2-naphthol (85-83-6). Gene mutation by the spot assay was performed for Sudan IV. Sudan IV was used at dose level of 200 µg/plate both with and without S9 metabolic activation system. The plates were incubated for 3 days at 37°C for the growth of colonies to occur. The plates were observed for an increase in the number of His+ revertants. The criteria adopted for scoring a mutagenic response in routine plate tests was that the observed number of revertants should exceed twice the background value for that given assay and exceed the 99.9% confidence limit based on our historical controls. Concurrent positive control was also included in the study.Sudan IV failed to induce mutation in Salmonellatyphimurium strain TA100, TA98, TA1535, TA1537 and TA1538 with and without S9 metabolic activation system in the spot test performed and hence is not likely to classify for gene mutation in vitro.

In a study for structurally and functionally similar read across chemical, Gene mutation toxicity study was performed by H. E. Seifried et al. (Chem. Res. Toxicol, 2006) to determine the mutagenic nature of C.I. Solvent orange 7 IUPAC: 1-[(2,4-dimethylphenyl)diazenyl]-2-naphthol (3118-97-6). The mutagenic potency of 1-(2,4-dimethylphenylazo)-2-naphthol (3118-97-6) was tested on theL5178Y TK+/-3.7.C mouse lymphoma cells. The test compound was found to be non-mutagenic when the mammalian cell was exposed for 4 hrs along with the total expression time of 48 hrs by using test concentration of 1.0– 349 µg/ml .The test compound induces no mutagenic response both in the presence and absence of metabolic activation system. Therefore 1-(2,4-dimethylphenylazo)-2-naphthol (3118-97-6) was considered to be non mutagenic in mammalian cell. Hence it is not likely to be classify as gene mutant in vitro.

 

 Based on the data available for the target chemical and its read across substance and applying weight of evidence 1,4-bis[(4-butylphenyl)amino]-5,8-dihydroxy-9,10-dihydroanthracene-9,10-dione (28198-05-2) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.

                                                                           

 

 

 

 

 

Justification for classification or non-classification

Thus based on the above annotation and CLP criteria for the target chemical .1,4-bis[(4-butylphenyl)amino]-5,8-dihydroxy-9,10-dihydroanthracene-9,10-dione (28198-05-2) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.