Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Proprietary GLP study, conducted according to EU guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Dimethylterephthalate, purity 99.99% (confirmed by GC-analysis), described as a white powder, batch no. 3633/81474.

Method

Target gene:
The study investigated histidine reversion in histidine-auxotrophic strains of Salmonella typhimurium.
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
S. typhimurium TA 1538
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Test concentrations with justification for top dose:
It was not possible to determine test concentrations in µg/plate (due to insolubility; see below).
Vehicle / solvent:
The test substance was not soluble in any of the commonly used solvents, therefore a Spot-Test was carried out.
Controlsopen allclose all
Untreated negative controls:
yes
Negative solvent / vehicle controls:
no
Remarks:
no solvent was used
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
Migrated to IUCLID6: TA98 and TA1538 without S9
Untreated negative controls:
yes
Negative solvent / vehicle controls:
no
Remarks:
no solvent was used
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
Migrated to IUCLID6: TA100 and TA1535 without S9
Untreated negative controls:
yes
Negative solvent / vehicle controls:
no
Remarks:
no solvent was used
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
Migrated to IUCLID6: TA1537 without S9
Untreated negative controls:
yes
Negative solvent / vehicle controls:
no
Remarks:
no solvent was used
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: aminoanthracene; TA100 with and without S9
Untreated negative controls:
yes
Negative solvent / vehicle controls:
no
Remarks:
no solvent was used
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
Migrated to IUCLID6: TA100 with and without S9
Details on test system and experimental conditions:
Bacterial counts were determined for each strain following overnight cultures.

Two Spot-Tests were carried out, with and without metabolic activation. A sterile microspatula was used to apply the test substance directly to the top agar (plated over minimal agar). Plates were incubated at 37.0-38.4°C. T
Evaluation criteria:
The number of revertant colonies were counted and compared to the natural reversion rate.
Statistics:
Statistical analysis was not performed beyong calculation of means and standard deviations.

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not applicable
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not applicable
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
There was no evidence of mutagenic activity in any strain, with and without metabolic activation.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

There was no evidence of mutagenic activity in any strain, with and without metabolic activation.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative with and without metabolic activation

There was no evidence of mutagenic activity in any strain, with and without metabolic activation.
Executive summary:
Dimethylterephthalate was tested in the Salmonella / microsome mutagenicity assay (Ames test), according to EU Method B.14. The test organisms were five histidine-auxotrophic (his-) Salmonella typhimurium strains (TA98, TA100, TA1535, TA1537 and TA1538).

 The substance was found to be insoluble in any of the prescribed Ames test solvents; therefore a Spot-Test was conducted. A sterile micro-spatula was used to apply the test substance to the top agar.  There was no evidence of mutagenic activity in any of the strains tested, with and without metabolic activation.