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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test conducted according to internationally accepted testing procedures and according to the GLP. The OECD recommended combination of strains was respected.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Method

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:
liver homogenate (S9 mix).
Test concentrations with justification for top dose:
50, 150, 500, 1500 and 500 µg/plate in both the experiments.
Vehicle / solvent:
Water for injection
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
mitomycin C
other: hydrazide sulphate, doxorubicine HCl monohydrate
Remarks:
TA 1335: HS 500 µg/plate; TA 1537 9-AA HCl 40 µg/plate in DMSO; TA 98 and TA 100 D HCl 4 µg/plate in DMSO; TA 102 M 5 µg/plate in DMSO.
Details on test system and experimental conditions:
Two independent experiments were performed. In both experiments the test item was dissolved in water for injection to obtain 50 mg/ml solution. An aliquot was further diluted to 15, 5, 1.5, 0.5 mg/ml.
Final tested concentration were 50, 150, 500, 1500 and 500 µg/plate in each experiment in each strain, three repetitions per dose.

The amino-acid requirements for growth were checked for each frozen stock culture preparation (histidine). The presence of characteristic mutations (i.e. rfa mutation in S. typhimurium through sensitivity to crystal violet, and uvrB mutation in S. typhimurium, through sensitivity to ultraviolet light).

The sterility checks on test item and S9 proved negative for bacterial growth.
Statistics:
Student's t test

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
Remarks:
no appreciable increase in the number of reversions in comparison with the negative control
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
at all the test article doses no significant cytotoxicity effects were observed
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Test article has shown no significant statistical variation of reverse mutation compared to negative controls, with and without metabolic activation
Positive controls were always within the accepted limits.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

No appreciable increase in the number of reversions in comparison with the negative control was evident at any of the concentration, with any strains, both in the presence and in the absence of metabolic activation. Furthermore, no significant cytotoxicity effects were observed.
Executive summary:

The mutagenic potential of test item was investigated using Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 as tester strains. The study was performed with and without liver homogenate (S9 mix). S9 mix consisted of S9 plus cofactors.

Two independent experiments were performed, setting up triplicate plates for each experimental point. In both experiments, five concentrations of the test item ranging from 50 up to 5000 µg/plate were tested.

At all the test article doses no significant cytotoxicity effects were observed, both with and without metabolic activation. As regards mutagenicity, was evident at any of the concentration, with any strains, both in the presence and in the absence of metabolic activation.

Conclusion

Non mutagen.