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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
Based on the prediction for in-vitro bacterial reverse mutation assay (e.g. Ames test) on S. typhimurium TA 1535 with or without S9 metabolic activation it was estimated that α,α-bis[4-(dimethylamino)phenyl]-4-(phenylamino)naphthalene-1-methanol was non mutagenic.
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)
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Reference:
Composition 0
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.1
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Test material information:
Composition 1
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
not specified
Vehicle controls valid:
not specified
Negative controls valid:
not specified
Positive controls valid:
not specified
Remarks on result:
other: all strains/cell types tested
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 6 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Similarity boundary:Target: c1(C(O)(c2c3c(c(Nc4ccccc4)cc2)cccc3)c2ccc(N(C)C)cc2)ccc(N(C)C)cc1
Threshold=50%,
Dice(Atom centered fragments)

Domain logical expression index: "b"

Similarity boundary:Target: c1(Nc2ccccc2)c2c(c(C(c3ccc(N(C)C)cc3)c3ccc(N(C)C)cc3)cc1)cccc2
Threshold=50%,
Dice(Atom centered fragments)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alcohol AND Aromatic amine AND Fused carbocyclic aromatic AND Naphtalene AND Overlapping groups by Organic functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alcohol AND Aromatic amine AND Aryl AND Fused carbocyclic aromatic AND Naphtalene by Organic functional groups

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Not categorized by OECD HPV Chemical Categories

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Maleic anhydride and acid OR Phosphonic acids - Group 2 OR Primary amines OR Secondary amines by OECD HPV Chemical Categories

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Similarity boundary:Target: c1(C(O)(c2c3c(c(Nc4ccccc4)cc2)cccc3)c2ccc(N(C)C)cc2)ccc(N(C)C)cc1
Threshold=30%,
Dice(Atom centered fragments)

Domain logical expression index: "j"

Similarity boundary:Target: c1(C(O)(c2c3c(c(Nc4ccccc4)cc2)cccc3)c2ccc(N(C)C)cc2)ccc(N(C)C)cc1
Threshold=10%,
Dice(Atom centered fragments)

Domain logical expression index: "k"

Similarity boundary:Target: c1(C(O)(c2c3c(c(Nc4ccccc4)cc2)cccc3)c2ccc(N(C)C)cc2)ccc(N(C)C)cc1
Threshold=40%,
Dice(Atom centered fragments)

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is >= 6.99

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.39

Conclusions:
Interpretation of results (migrated information):
negative

Based on the prediction for in-vitro bacterial reverse mutation assay (e.g. Ames test) on S. typhimurium TA 1535 with or without S9 metabolic activation it was estimated that α,α-bis[4-(dimethylamino)phenyl]-4-(phenylamino)naphthalene-1-methanol was non mutagenic.
Executive summary:

Based on the prediction for in-vitro bacterial reverse mutation assay (e.g. Ames test) on S. typhimurium TA 1535 with or without S9 metabolic activation it was estimated that α,α-bis[4-(dimethylamino)phenyl]-4-(phenylamino)naphthalene-1-methanol was non mutagenic.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

The summary of the results are presented below

 

Sr.No

Endpoint

Interpretation of results

Species

Sources

1

Genetic toxicity

Negative with and without metabolic activation

Salmonella typhimurium strain TA1537,

Predicted data

2

Genetic toxicity

negative with metabolic activation

S. typhimuriumTA97, TA98, TA100, TA102, TA104, or TA1535

RA Publication data

3

Genetic toxicity

Negative with and without metabolic activation

Chinese hamster Ovary (CHO)

RA Publication data

 

By applying weight of evidence approach it was concluded that the test substance α,α-bis[4-(dimethylamino)phenyl]-4-(phenylamino)naphthalene-1-methanol shows negative results in Salmonella typhimurium & Chinese hamster Ovary.


Justification for selection of genetic toxicity endpoint
Model considered reliable by OECD

Justification for classification or non-classification

Based upon the prediction done using QSAR, it can be concluded that the α,α-bis[4-(dimethylamino)phenyl]-4-(phenylamino)naphthalene-1-methanol (Solvent Blue 4) is not likely to be mutagenic to bacteria as well as cause chromosomal abberation on Chinese hamster Lung (CHL) without S9 metabolic activation. Thus, the chemical is classified as non-mutagenic in the dose levels mentioned in the predictions.