Spinflam MF 83 PP-25

Genetic toxicity: in vitro

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.