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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:
from 13th of August to 28th of November, 1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Test conducted in GLP according to the version of the OECD guideline 471 applicable then. However under the currently version of the guideline it is also required to include Salmonella typhimurium TA102 and/or Escherichia coli WP2 or E.coli WP2 (pKM101)

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

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:
1st experiment: 8; 40; 200; 1000 and 5000 µg/plate
2nd experiment: 5, 10, 20, 50 and 100 µg/plate
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
DMSO and the untreated fresh cell suspensions served as negative control
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
sodium azide
other: 4-nitro-o-phenylendiamine
Remarks:
As positive controls, sodium azide was used in the tester strains TA 100 and TA 1535, 9-aminoacridine in the tester strain TA 1537, and 4-nitro-o-phenylendiamine in the tester strains TA 98 and TA 1538 without microsomal drug-metabolizing enzymes (S9-mix)
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
DMSO and the untreated fresh cell suspensions served as negative control
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: The enzyme activity of the Aroclor 1254 induced S9 fractions was controlled by testing with 2-aminoanthracene in all strains.
Remarks:
The enzyme activity of the S9 fractions was controlled by testing with 2-aminoanthracene in all strains.

Results and discussion

Test resultsopen allclose all
Key result
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:
cytotoxicity
Remarks:
see table 1, 2 & 3
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
see table 1, 2 & 3
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
The test item was tested in two independent test series at a concentration range of 5.0 - 5000 µg/plate (first and second test).
The test item was tested in the absence and presence of Aroclor 1254-induced S9-mix. In both test series (Tables 1 - 2) the plates were incubated for 48 hours at 37° C.
The findings show that the test item did not induce any reverse mutations in the absence of rat liver enzymes (without S9-mix), nor did occur any induced reverse mutations in the presence of Aroclor 1254-induced S9-mix (with S9-mix).

Toxic effects were noted, starting at a concentration of 40 µg/plate without S9-mix and above 200 µg/plate with S9-mix. Precipitations were not noted. The summarized results are presented in table 3.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
In the described mutagenicity test and under the experimental conditions reported, the test item did not induce point mutations by base-pair changes or frameshifts in the genome of the strains used.
Therefore the test item is not considered to be mutagenic in this Salmonella typhimurium reverse mutation assay.
Executive summary:

In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the test item did not induce point mutations by base-pair changes or frameshifts in the genome of the strains used.

Therefore, the test item is not considered to be mutagenic in this Salmonella typhimurium reverse mutation assay.