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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
(Q)SAR
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1986 and 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
The analogue approach was chosen as a suitable method for read-across since the target molecule, 1,5-dinitronapthalene, was not found in any of the existing chemical categories searchable in the following databases -US EPA, OECD, eChemPortal and OECD QSAR Toolbox.
Following that decision, the selection of suitable analogues for the molecule of interest involved the use of structural similarity analysis. These analyses were conducted in the ChemIDplus portal and relied on a quantitative measurement (scored between 0 and 1) after the evaluation of molecules with a structural similarity higher than 95% by the Tanimoto index.

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
Guideline not specified, summary data from read-across report. These data were peer-reviewed and considered acceptable.
GLP compliance:
not specified
Remarks:
Read-across endpoint is taken from a collection of data - the GLP compliance is not specified. Studies were conducted in 1986 and 1994.
Type of assay:
other: read-across to multiple studies: In vitro Ames; In Vivo test Drosophilia; Bacterial mutagenicity ISSSTY

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Specific details on test material used for the study:
Read-across molecule, test material specifics are not available.

Method

Target gene:
Not specified
Species / strain
Species / strain / cell type:
bacteria, other: bacteria, strain not specified
Additional strain / cell type characteristics:
not specified
Metabolic activation:
not specified
Controls
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
not specified
Remarks:
Data from read-across summary, controls not specified
Details on test system and experimental conditions:
Results taken from read-across to multiple studies.

Results and discussion

Test results
Key result
Species / strain:
bacteria, other: not specified
Metabolic activation:
not specified
Genotoxicity:
positive
Remarks:
Read-across, detail not available
Cytotoxicity / choice of top concentrations:
not specified
Remarks:
Read-across, detail not available
Vehicle controls validity:
not specified
Remarks:
Read-across, detail not available
Untreated negative controls validity:
not specified
Remarks:
Read-across, detail not available
Positive controls validity:
not specified
Remarks:
Read-across, detail not available
Remarks on result:
other: Positive results in vitro were supported by a positive result in vivo, by a somatic cell test, is considered as evidence to classify when relying on in silico data. Therefore, it is acceptable to classify the substance of interest as a Mutagen Category 2.

Any other information on results incl. tables

Positive in vitro data in the bacterial system (Ames test) is available from the searchable databases for both target and source substances. Peer-reviewed, non-standardised data were considered acceptable for the current evaluation (original publications of Mortelmans et al., 1986 and Mersch-Sunderman et al., 1994).

In vivo mutagenicity potential was also reported in somatic cells of Drosophila for both target and source molecules. The results of the “Wing somatic mutation and recombination”- SMART test in Drosophila revealed that both compounds can cause genetic toxicity by eliciting an increased incidence of homologous somatic recombination. Specifically, 1-nitro-naphthalene was the compound with the strongest genotoxicity and 1,5-dinitronapthalene approximately 333 times less potent than this compound. (original data, peer-reviewed studies (standard), authors Delgado-Rodriguez et al., 1995 available at HSDB database)

The fact that positive results in vitro were supported by a positive result in vivo, by a somatic cell test, is considered by ECHA as enough evidence to lead to classification when the assessment relies upon in silico data. Therefore, it is acceptable to classify the substance of interest as a Mutagen Category 2.

Applicant's summary and conclusion

Conclusions:
Positive in vitro data in the bacterial system (Ames test) is available from the searchable databases for both target and source substances. Peer-reviewed, non-standardised data were considered acceptable for the current evaluation (original publications of Mortelmans et al., 1986 and Mersch-Sunderman et al., 1994).
In vivo mutagenicity potential was also reported in somatic cells of Drosophila for both target and source molecules. The results of the “Wing somatic mutation and recombination”- SMART test in Drosophila revealed that both compounds can cause genetic toxicity by eliciting an increased incidence of homologous somatic recombination. Specifically, 1-nitro-naphthalene was the compound with the strongest genotoxicity and 1,5-dinitronapthalene approximately 333 times less potent than this compound. (original data, peer-reviewed studies (standard), authors Delgado-Rodriguez et al., 1995 available at HSDB database)
The fact that positive results in vitro were supported by a positive result in vivo, by a somatic cell test, is considered by ECHA as enough evidence to lead to classification when the assessment relies upon in silico data. Therefore, it is acceptable to classify the substance of interest as a Mutagen Category 2.
Executive summary:

Positive in vitro data in the bacterial system (Ames test) is available from the searchable databases for both target and source substances. Peer-reviewed, non-standardised data were considered acceptable for the current evaluation (original publications of Mortelmans et al., 1986 and Mersch-Sunderman et al., 1994).

In vivo mutagenicity potential was also reported in somatic cells of Drosophila for both target and source molecules. The results of the “Wing somatic mutation and recombination”- SMART test in Drosophila revealed that both compounds can cause genetic toxicity by eliciting an increased incidence of homologous somatic recombination. Specifically, 1-nitro-naphthalene was the compound with the strongest genotoxicity and 1,5-dinitronapthalene approximately 333 times less potent than this compound. (original data, peer-reviewed studies (standard), authors Delgado-Rodriguez et al., 1995 available at HSDB database)

The fact that positive results in vitro were supported by a positive result in vivo, by a somatic cell test, is considered by ECHA as enough evidence to lead to classification when the assessment relies upon in silico data. Therefore, it is acceptable to classify the substance of interest as a Mutagen Category 2.