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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The substance was reliably predicted to be mutagenic by QSAR models, but on the basis of the results of the Bacterial Reverse Mutation Assay carried out according to OECD 471, the substance resulted to be NOT MUTAGENIC.

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
(Q)SAR
Adequacy of study:
other information
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 adequate and reliable documentation / justification
Justification for type of information:
Documentation about the justification is provided in attachment (See supporting information). The reliability assessment of the prediction is presented in the attached document as well (QPRF). QSAR model reporting format is presented in the QMRF file attached.
Qualifier:
equivalent or similar to guideline
Guideline:
other: ECHA guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals.
Principles of method if other than guideline:
- Ferrari T., Gini G. An open source multistep model to predict mutagenicity from statistical analysis and relevant structural alerts. Chemistry Central Journal (2010), 4
(Suppl 1):S2
- Benigni R., Bossa C., Jeliazkova N.G., Netzeva T.I., Worth A.P. The Benigni/Bossa rulebase for mutagenicity and carcinogenicity - a module of toxtree. Technical Report EUR 23241 EN, European Commission - Joint Research Centre 2008.
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
O=C(N1C2=CC=CC=C2CCC3=C1C=C([N+]([O-])=O)C=C3)C
Remarks on result:
mutagenic potential (based on QSAR/QSPR prediction)

The prediction was deemed to be reliable on the basis of the parameters listed above. The molecule falls into the applicability domain of the model.

Conclusions:
The molecule was predicted to be mutagenic.
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
(Q)SAR
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
Documentation about the justification is provided in attachment (See supporting information). The reliability assessment of the prediction is presented in the attached document as well (QPRF).
Qualifier:
equivalent or similar to guideline
Guideline:
other: ECHA guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals.
Principles of method if other than guideline:
- Benigni, R., Bossa, C. “Mechanisms of chemical carcinogenicity and mutagenicity: a review with implications for predictive toxicology”, Chem. Revs. 111 (2011), 2507-2536; -
- Benigni, R., Bossa C., Tcheremenskaia O. “In vitro cell transformation assays for an integrated, alternative assessment of carcinogenicity: a databased analysis”, Mutagenesis (2013), 28(1):107-16.
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
O=C(N1C2=CC=CC=C2CCC3=C1C=C([N+]([O-])=O)C=C3)C
Remarks on result:
mutagenic potential (based on QSAR/QSPR prediction)

The prediction was deemed to be reliable on the basis of the parameters listed above. The molecule partially falls into the applicability domain of the model.

Conclusions:
The molecule was predicted to be mutagenic.
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
(Q)SAR
Adequacy of study:
other information
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 adequate and reliable documentation / justification
Justification for type of information:
Documentation about the justification is provided in attachment (See supporting information). The reliability assessment of the prediction is presented in the attached document as well (QPRF).
Qualifier:
equivalent or similar to guideline
Guideline:
other: ECHA guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals.
Principles of method if other than guideline:
T. Ferrari, D. Cattaneo, G. Gini, N. Golbamaki Bakhtyari, A. Manganaro, E. Benfenati, “Automatic knowledge extraction from chemical structures: the case of mutagenicity prediction”, SAR and QSAR in Environmental Research (2013), vol. 24 issue 5, 365-83.
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
O=C(N1C2=CC=CC=C2CCC3=C1C=C([N+]([O-])=O)C=C3)C
Remarks on result:
mutagenic potential (based on QSAR/QSPR prediction)

The prediction was deemed to be reliable on the basis of the parameters listed above. The molecule falls into the applicability domain of the model.

Conclusions:
The molecule was predicted to be mutagenic.
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
1997
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
3-Nitro-5-Acetyl Iminodibenzyl
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Metabolic activation:
with and without
Metabolic activation system:
The enzymatic for metabolism activation (S9 mix) was prepared according to Manufacturer procedure: Regensys A has been completed by the addition of Regensys B, then 5 ml of S9 have been added to obtain a S9 mix solution at 10%.
Untreated negative controls:
no
Negative solvent / vehicle controls:
no
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
sodium azide
cyclophosphamide
mitomycin C
other: Daunomycin, 2 Aminoantracene
Details on test system and experimental conditions:
The whole essay was performed in triplicate.
Key result
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
True negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
True negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
True negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
True negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
True negative controls validity:
valid
Positive controls validity:
valid
Conclusions:
On the basis of the results interpreted according to OECD 471:1997, the substance 3-Nitro-5-Acetyl Iminodibenzyl tested as recommended by standards, proved to be NOT MUTAGENIC for all the test strains, either in the presence or absence of metabolic activation.
Executive summary:

The bacterial reverse mutation assay was performed on five mutant strains of Salmonella typhimurium (TA 1535, TA 1537, TA 98, TA 100, TA 102).

The presumed mutagenic activity of the test substance was determined by comparing number of reverting colonies in treated cultures with the number of the reverting organisms in the control cultures.

The direct incorporation method in a plate was used both in the presence of, and without, an enzymatic system for metabolic activation.

The test substance was prepared as solution in water with a concentration equivalent to 50 mg/ml and 4 different concentrations of semi-log intervals between them were prepared.

On the basis of the results interpreted according to OECD 471: 1997, the test substance 3-Nitro-5-Acetyl Iminodibenzyl tested as recommended by standards, proved to be NOT MUTAGENIC for all the test strains, either in the presence or absence of metabolic activation.

Additional information

Justification for classification or non-classification

On the basis of the results of the Bacterial Reverse Mutation Assay, the substance resulted to be NOT MUTAGENIC. However, the available data are not sufficient to conclude on the classification for this hazard class according to CLP.