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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Principles of method if other than guideline:
The test item Phthalic Anhydride was assessed for its potential to induce mutations at the HPRT locus using V79 cells of the Chinese Hamster.
The selection of the concentrations was based on data from the pre-experiments. In all experiments 10 mM was selected as the highest
concentration.
The test item was investigated at the following concentrations:
Experiment I
with metabolic activation: 0.10,0.25,0.5,1.0,2.5,5.0,7.5 and 10 mM
and without metabolic activation: 0.025,0.05,0.5, 1.0,2.5,5.0, 7.5 and 10 mM
Experiment II
without metabolic activation: 0.10,0.25,0.5,1.0,2.5,5.0,7.5 and 10 mM
and with metabolic activation: 1.0,1.75,2.5,4.0,5.5,7.0,8.5 and 10 mM
GLP compliance:
yes (incl. certificate)
Type of assay:
mammalian cell gene mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
purity: > 99%

Method

Target gene:
no data
Species / strain
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Test concentrations with justification for top dose:
Experiment I
with metabolic activation: 0.10,0.25,0.5,1.0,2.5,5.0,7.5 and 10 mM
and without metabolic activation: 0.025,0.05,0.5, 1.0,2.5,5.0, 7.5 and 10 mM
Experiment II
without metabolic activation: 0.10,0.25,0.5,1.0,2.5,5.0,7.5 and 10 mM
and with metabolic activation: 1.0,1.75,2.5,4.0,5.5,7.0,8.5 and 10 mM
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
yes
Positive controls:
yes
Positive control substance:
other: Ethylmethanesulfonate; 7,12-Dimethylbenz(a)anthracene

Results and discussion

Test results
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: other: V79cells
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

No precipitation of the test item was noted in the experiments.

No biologically relevant growth inhibition was observed in experiment I and II with and without metabolic activation with one exception. In experiment II without metabolic activation for the highest concentration evaluated (l0 mM) the relative growth was 17.6%.

In both experiments no biologically relevant increase of mutants was found after treatment with the test item (with and without metabolic activation). No dose-response relationship was observed.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative
Executive summary:

The test item Phthalic Anhydride was assessed for its potential to induce mutations at the HPRT locus using V79 cells of the Chinese Hamster up to concentrations of 10mM.

Result: negative, with and without metabolic activation.