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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:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline GLP study with full report available

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.5265 (The Salmonella typhimurium Bacterial Reverse Mutation Test)
Deviations:
no
Qualifier:
according to
Guideline:
JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Durasyn 124
- Lot/batch No.: J900-001-1
- Storage condition of test material: room temperature in the dark

Method

Target gene:
Target gene identity not required to characterise test system.
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
E. coli WP2 uvr A
Metabolic activation:
with and without
Metabolic activation system:
rat liver homogenate (10% liver S9 in standard co-factors
Test concentrations with justification for top dose:
0, 50, 150, 500, 1500, 5000 ug/plate
Vehicle / solvent:
Tetrahydrofuran
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: Without metabolic activation: N-ethyl-n'-nitro-N-nitrosoguanidine (For TA100, TA1535, WP2uvrA-), 9-aminoacridine (TA1537), Ninitroquinoline-1-oxide (TA98). With metabolic activation: Benzo(a)opyrene (TA98), 2-aminoanthracene (all others).
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 hours at 37C

NUMBER OF REPLICATIONS: 3 and experiment repeated a second time using fresh cultures of the bacterial strains and fresh test material formulations.

OTHER: Experimental phase: 23/1/08 - 13/2/08
Evaluation criteria:
Dose related increase in revertant frequency and/or a reproducible increase at one or more concentrations. Statistical significance and biological relevance of such findings taken into account. If such findings are found and considered relevant, the substance is considered mutagenic (positive.)
Statistics:
mean and standard deviation.

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:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: Globular precipitation observed at and above 1500ug/plate but this did not prevent scoring of revertant colonies.

RANGE-FINDING/SCREENING STUDIES: Using E coli and TA100 at 10 doses up to 5000ug/plate. Negative

COMPARISON WITH HISTORICAL CONTROL DATA: All doses and controls within historic control ranges.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

In experiment 1, the 1500ug/plate dose with TA100 showed statistically significantly raised reversion rates compared to the concurrent solvent control in a single replicate. Since this was not repeated in either of the other two replicates or in experiment 2 and was within historic control ranges, it was regarded as random and not of biological significance.

Applicant's summary and conclusion

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

The substance is not mutagenic in bacteria.
Executive summary:

In a guideline GLP Ames study, the substance did not produce toxicologically significant elevated counts of revertant colonies in any of the five bacterial strains tested (TA98, TA100, TA1535, TA1537 and WP2uvra-) at doses up to 5000ug/plate, with and without S9 metabolic activation. At levels of 1500ug/plate and above there was evidence that the solubility limit had been exceeded in the system. All positive controls responded as expected.

Synopsis:

Not mutagenic