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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:
2 (reliable with restrictions)

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
and EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The aim of the sudy was to compare two batches.
Batch No.: M06015/001 (chemical purity: 100.8%); Batch No.: 20098/A8DRT022B (chemical purity of 101.0%).

Method

Target gene:
histidine
Species / strain
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Metabolic activation system:
Arochlor induced rat liver S9 , final concentration: 0.8 % (v/v) S9
Test concentrations with justification for top dose:
The tested concentrations of Menaphtacyan used were selected from a previous study. (GERVAIS V. and Delongeas J-L (2006) Menaphtacyan Genotoxicity study: Detection of Reverse Mutation in histidine-requiring TA1537 Salmonella typhimurium (Ames test). Biologie Servier Internal report No. 5731.
Vehicle:
Dimethyl sulphoxide (DMSO)
Controls
Negative controls:
no
Solvent controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
Migrated to IUCLID6: and 2-anthramine
Details on test system and conditions:
-direct plating preincubation
-independent experiments-triplicates/concentrations
Evaluation criteria:
-genotoxicity (bacterial lawn and number of revertants)
-genotoxictity (number of revertants)
Statistics:
Statistical analysis using automated decision tree.
For positive control, Student t test versus vehicle control on square root data.

Results and discussion

Test results
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
other: generally from 250 μg/plate
Vehicle controls valid:
yes
Negative controls valid:
not examined
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Additional information on results:
Genotoxic effects:
Slight, isolated but statistically significant increase in the numbers of revertant colonies was noted for the batch M06015/001 at 125 μg/plate in the direct plating method without methabolic activation. As this increase was not concentration related, did not reach 3.0-fold the solvent control and remained near the highest value of our historical data (18 versus 17), the M06015/001 was considered as devoid of mutagenic potential.
No increase was noted in with the batch 20098A8DRT022B. In conclusion no genotoxic effects was observed with both batches.

Cytotoxic effects:
For both batches, a reduction in size of colonies was noted from 250 μg/plate with and without metabolic activation, reaching a reduction in the numbers of colonies at 1000 μg/plate. Clearing of the bacterial lawn was noted at 1000 μg/plate without metabolic activation and from 500 μg/plate with metabolic activation.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative in TA1537

In conclusion no genotoxic effects was observed with both batches.