4-acetyl-1-methylpyridinium 4-methylbenzenesulfonate

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: Guideline study and GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

[TN]Gro 266[/TN][SPEC][/SPEC][AM]>99%[/AM]

IUPAC Name:

[TN]Gro 266[/TN][SPEC][/SPEC][AM]>99%[/AM]

Constituent 2

Reference substance name:

4-acetyl-1-methylpyridin-1-ium 4-methylbenzene-1-sulfonate

EC Number:

700-195-9

Cas Number:

223398-24-1

Molecular formula:

C8 H10 N O . C7 H7 O3 S

IUPAC Name:

4-acetyl-1-methylpyridin-1-ium 4-methylbenzene-1-sulfonate

Details on test material:

GRO 266
SAT 080010
Batch No.: Gro-Rn-9810-003

Method

Species / strain

Species / strain / cell type:

other: Salmonella typhimurium: TA 1535, TA 1537, TA 98, TA 100 and TA 102

Additional strain / cell type characteristics:

other: not applicable

Metabolic activation:

with and without

Metabolic activation system:

rat liver S9 induced

Test concentrations with justification for top dose:

Experiment I: 3, 10, 33, 100, 333, 1000, 2500 and 5000 µg/plate
Experiment II: 33, 100, 333, 1000, 2500 and 5000 µg/plate

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: see remarks

Remarks:

-S9: Sodium Azide, 4-NOPD, MMS; +S-9: 12-Aminoanthracene, 2-AA

Details on test system and experimental conditions:

Method of application: in medium; in agar (plate incorporation); preincubation; suspension

Number of replications: 3 plates

Evaluation criteria:

A test item is considered as a mutagen if a biologically relevant increase in the number of revertants exceeding the treshold of twice (strains TA 98, TA 100 and TA 102) or thrice (strains TA 1535 and TA 1537) the colony count of the corresponding solvent control is observed.
A dose dependent increase is considered biologically relevent if the treshold is exceed at more than one concentration.
An increase exceeding the treshold at only one concentration is judged as biologically relevant if reproduced in an independent second
experiment.
A dose dependent increase in the number of revertant colonies below the treshold is regarded as an indication of a mutagenic potential if reproduced in an independent second experiment. Howewer, whenever the colony counts remain within the historical range of negative and solvent
controls such an increase is not considered biologically relevant.

Statistics:

According to the OECD guideline 471, a statistical analysis of the data is not mandatory.

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100, TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

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

In conclusion, It can be stated that during the described mutagenicity test and under the experimental conditions reported, the test item did not
induce gene mutatuions by base pair changes or frameshift in the genome of the strains used.
Therefore, GRO 266 is consideed to be non-mutagenic in this Salmonella typhimurium reverse mutation assay.

Executive summary:

This study was performed to investigate the potential of GRO 266 to induce gene mutations according to the plate incorporation test (experiment I) and the pre-incubation test (experiment II) using the Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100, TA 102.

The assay was performed in two independent experiments both with and without liver microsomal activation. Each concentration, including the controls, was tested in triplicate. The test item was tested at the following concentrations:

Pre-Experiment/Experiment I: 3, 10, 33, 100, 333, 1000, 2500 and 5000 µg/plate

Experiment II: 33, 100, 333, 1000, 2500 and 5000 µg/plate

The plates incubated with the test item showed normal backround growth up to 5000 µg/plate with and without S9 mix in all strains used.

No toxic effects, evident as a reduction in the number of revertants (below the indication factor of 0.5), occured in the test groups with and without metabolic activation.

No substantial increase in relevant colony numbers of any of the five tester strains was observed following treatment with GRO 266 at any dose level, neither in the presence nor absence of metabolic activation (S9 mix). There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological relevance.

Appropriate reference mutagens were used as positive controls and showed a distinct increase of induced revertant colonies.