2-octadecyl-1H-thioxantheno[2,1,9-def]isoquinoline-1,3(2H)-dione

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The test chemical 2-octadecyl-1H-thioxantheno[2,1,9-def]isoquinoline-1,3(2H)-dione is not likely to be a gene mutant in vitro.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from prediction model

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Target gene:

No data

Species / strain / cell type:

S. typhimurium TA 100

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with

Metabolic activation system:

S9 activation system

Test concentrations with justification for top dose:

No data

Vehicle / solvent:

No data

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Positive control substance:

not specified

Remarks:

No data

Details on test system and experimental conditions:

No data

Evaluation criteria:

No data

Statistics:

No data

Species / strain:

S. typhimurium TA 100

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:

No data

Remarks on result:

other: strain/cell type:

Remarks:

Migrated from field 'Test system'.

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" )  and ("j" and ( not "k") )  )  and ("l" and "m" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aryl AND Biphenyl AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Imide AND Naphtalene AND Quinolone/ Quinolinedione/ Isoquinolinedione AND Sulfide by Organic Functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives AND SN1 AND SN1 >> Alkylation after metabolically formed carbenium ion species AND SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives AND SN2 AND SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation AND SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Iminium Ion Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

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, NH2 group OR 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, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (extension) ONLY

Domain logical expression index: "i"

Similarity boundary:Target: CCCCCCCCCCCCCCCCCCN1C(=O)c2ccc3c4c2c(ccc4-c2ccccc2S3)C1=O
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Stable form by Tautomers unstable

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Conjugated keto(scy) - 1,5-H shift OR Imine form - 1,3-H shift OR Ketohydrazone form - 1,5-H shift OR Polycyclic aromatic hydrocarbons (PAHs) by Tautomers unstable

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is >= 9.79

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= 15.2

Conclusions:

Interpretation of results (migrated information):
negative with metabolic activation

The test compound 2-octadecyl-1H-thioxantheno[2,1,9-def]isoquinoline-1,3(2H)-dione failed to induce mutation in the Salmonella typhimurium strain TA100 with S9 activation system and hence is negative for gene mutation in vitro.

Executive summary:

Gene mutation was estimated for the test compound 2-octadecyl-1H-thioxantheno[2,1,9-def]isoquinoline-1,3(2H)-dione using SSS QSAR prediction database, 2016. The test assumed the use of Salmonella typhimurium TA100 with S9 activation system. The test compound 2-octadecyl-1H-thioxantheno[2,1,9 -def]isoquinoline-1,3(2H)-dione failed to induce mutation in the Salmonella typhimurium strain TA100 with S9 activation system and hence is negative for gene mutation in vitro. Thus the chemical is not likely to be a gene mutant in vitro.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Gene toxicity in vitro:

Prediction model based estimation and data from read across have been summarized to determine the mutagenic nature of the test compound in vitro:

Gene mutation was estimated for the test compound 2-octadecyl-1H-thioxantheno[2,1,9-def]isoquinoline-1,3(2H)-dione (CAS no 27870 -92 -4) using SSS QSAR prediction database, 2016. The test assumed the use of Salmonella typhimurium TA100 with S9 activation system. The test compound 2-octadecyl-1H-thioxantheno[2,1,9 -def]isoquinoline-1,3(2H)-dione failed to induce mutation in the Salmonella typhimurium strain TA100 with S9 activation system and hence is negative for gene mutation in vitro. Thus the chemical is not likely to be a gene mutant in vitro.

Gene mutation was estimated for the test compound 2-octadecyl-1H-thioxantheno[2,1,9-def]isoquinoline-1,3(2H)-dione (CAS no 27870 -92 -4) using SSS QSAR prediction database, 2016. The test assumed the use of Salmonella typhimurium TA1535 without S9 activation system. The test compound 2-octadecyl-1H-thioxantheno[2,1,9 -def]isoquinoline-1,3(2H)-dione failed to induce mutation in the Salmonella typhimurium strain TA1535 without S9 activation system and hence is negative for gene mutation in vitro. Thus the chemical is not likely to be a gene mutant in vitro.

Based on the QSAR prediction done using the Danish (Q)SAR Database (2016), the genetic toxicity was estimated to be negative on S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 for 2-octadecyl-1H-thioxantheno[2,1,9-def]isoquinoline-1,3(2H)-dione (CAS no 27870 -92 -4) in an Ames test. Thus it can be concluded that the substance 2-octadecyl-1H-thioxantheno[2,1,9-def]isoquinoline-1,3(2H)-dione is likely to be negative for genetic toxicity in vitro.

Salmonella/microsome test in the absence of exogenous metabolic activation and in the presence of liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters was performed by Zeiger et al (1987) to evaluate the mutagenic nature of the test compound 2-Heptadecyl-4,5-dihydro-1H-imidazole (RA CAS no 95 -19 -2). The test compound was used at a dosage level of 0.0, 0.030, 0.100, 0.300, 1.0000, 2.200, 3.300, 10.000, 33.000, 100.000 µg/plate in the preincubation assay of 48 hrs. 2-Heptadecyl-4,5-dihydro-1H-imidazolefailed to induce mutation in the S. typhimurium tester strains TA 1535, TA 1537, TA 98 and TA 100 and hence is negative for mutation in vitro.

Salmonella mutagenicity test was performed by Bartsch et al (1977) to determine the mutagenic nature of the test compound N-Myristoyloxy-N-acetyl-2-aminofluorene (RA CAS no 63224 -44 -2) and N-Myristoyloxy-N-myristoyl-2-aminofluorene (RA CAS no 63224 -46 -4) . The test compound was tested using S. typhimurium strains TA1538, TA100, and TA98 at dose levels of upto 2000 nmoles/plate. After 48 hrs exposure period, increase in the number of his⁺revertants was counted. The test compound N-Myristoyloxy-N-acetyl-2-aminofluorene and N-Myristoyloxy-N-myristoyl-2-aminofluorene failed to induce mutation in the S. typhimurium strains TA1538, TA100, and TA98 and is likely to be negative for gene mutation in vitro. Very little mutagenicity was noted for strain TA100 at levels up to 100 nmoles/plate.

Based on the weight of evidence data summarized, even though very little mutagenicity is noted for the RA CAS no 63224 -44 -2 and RA CAS no 63224 -46 -4 in the Salmonella typhimurium strain TA100 but both the chemicals are not likely to be mutagenic in the tester strains TA98 and TA1538. Using the weight of evidence approach, the test chemical 2-octadecyl-1H-thioxantheno[2,1,9-def]isoquinoline-1,3(2H)-dione (CAS no 27870 -92 -4) is not likely to be mutagenic in vitro.

 

Justification for selection of genetic toxicity endpoint
Data is from prediction database

Justification for classification or non-classification

Using the weight of evidence approach, the test chemical 2-octadecyl-1H-thioxantheno[2,1,9-def]isoquinoline-1,3(2H)-dione (CAS no 27870 -92 -4) is not likely to be a gene mutagen in vitro.

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