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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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From December 14 to 22, 1995
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
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
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): EUCAROL APG/SS
- Physical state: liquid (aqueous solution 45% w/v)
- Lot/batch No.: 1953/I
- Expiration date of the lot/batch: May 26, 1996
- Storage condition of test material: at room temperature

Method

Target gene:
histidine
Species / strain
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:
S9 Mix
Test concentrations with justification for top dose:
First exp: 50, 150, 500, 1500 and 5000 ug/plate were tested
Second exp: 15, 50, 150, 500 and 1500 ug/plate were tested
Triplicate plates for each experimental point.
Vehicle / solvent:
water for injection
Controls
Untreated negative controls:
yes
Remarks:
solvent
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
other: hydrazine sulphate, 9-aminoacridine HCl monohydrate, Mitomycin C, Doxorubicine HCl, 2-aminoanthracene and 2-aminofluorene

Results and discussion

Test results
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 1500 ug/plate slightly cytotoxic
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

The sterility checks with the compound proved negative for bacterial growth.

All the strains used proved sensitive to crystal violet.ùAmpicillin inhibited the growth of TA1535, TA1537 strains but did not inhibit that of the other strains.

In the first experiment, at 5000 ug/plate both with and without metabolic activation, the test article proved to be severely cytotoxic on the test system, making impossible the revertant colony growth. At 1500 ug/plate the test article proved to be slightly cytotoxic giving statistical significant reduction of revertant colony growth in comparison with the negative control.

In the second experiment again slight cytotoxic effects were observed at 1500 ug/plate, with and without metabolica activation, giving reduction in the number of revertant colonies in comparison with the negative control.

As regards mutagenicity, no appreciable increase in the number of reversions in comparison with the negative control was evident in either experiment at any of the doses for any strain, with or without metabolic activation.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

In the concentration range investigated, the test substance did not show any mutagenic activity with or without the addition of S9 liver homogenate fractions.