[2,2,6,6-tetramethyl-4-(trimethylazaniumyl)piperidin-1-yl]oxidanyl chloride

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

One bacterial reverse mutation test was performed with the test material TMA-Tempo. This test did not indicate mutagenic properties of the test material under the test conditions.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09.03.2018 to 26.04.2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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

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:

S9 mix

Test concentrations with justification for top dose:

31.6, 100, 316, 1000, 2500 and 5000 μg/plate

Vehicle / solvent:

purified water

Untreated negative controls:

yes

Remarks:

purified water

Negative solvent / vehicle controls:

yes

Remarks:

purified water

Positive controls:

yes

Remarks:

without metabolic activation

Positive control substance:

sodium azide

Remarks:

Strain TA100 (10µg/plate) and TA1535 (10µg/plate)

Positive controls:

yes

Remarks:

without metabolic activation

Positive control substance:

other: 4-NOPD; 4-nitro-o-phenylene-diamine

Remarks:

Strain TA98 (10µg/plate) and TA1537 (40µg/plate)

Positive controls:

yes

Remarks:

without metabolic activation

Positive control substance:

methylmethanesulfonate

Remarks:

Strain TA102 (1µg/plate)

Positive controls:

yes

Remarks:

with metabolic activation

Positive control substance:

other: 2-AA; 2-aminoanthracene

Remarks:

Strain TA98, TA100, TA1535, TA1537 (all 2.5µg/plate) and TA102 (10µg/plate)

Details on test system and experimental conditions:

The test item TMA-TEMPO was investigated for its potential to induce gene mutations according to the plate incorporation test (experiment I) and the pre-incubation test (experiment II) using Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA102.
In two independent experiments several concentrations of the test item were used. Each assay was conducted with and without metabolic activation. The concentrations, including the controls, were tested in triplicate.

Evaluation criteria:

The Mutation Factor is calculated by dividing the mean value of the revertant counts by the mean values of the solvent control (the exact and not the rounded values are used for calculation).
A test item is considered as mutagenic if:
- a clear and dose-related increase in the number of revertants occurs and/or
- a biologically relevant positive response for at least one of the dose groups occurs
in at least one tester strain with or without metabolic activation.

A biologically relevant increase is described as follows:
- if in tester strains TA98, TA100 and TA102 the number of reversions is at least twice as high
- if in tester strains TA1535 and TA1537 the number of reversions is at least three times higher
than the reversion rate of the solvent control

Key result

Species / strain:

S. typhimurium, other: TA98, TA100, TA1535, TA1537, TA102

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

Additional information on results:

No precipitation of the test item was observed in any tester strain used in experiment I and II (with and without metabolic activation).
No toxic effects of the test item were noted in any of the five tester strains used up to the highest dose group evaluated with and without metabolic activation in experiment I and II.

Conclusions:

In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, TMA-TEMPO did not cause gene mutations by base pair changes or frameshifts in the genome of the tester strains used.
Therefore, TMA-TEMPO is considered to be non-mutagenic in this bacterial reverse mutation assay.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Justification for classification or non-classification

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

Therefore, TMA-TEMPO is considered to be non-mutagenic in this bacterial reverse mutation assay and requires no classification for germ cell mutagenicity according to CLP Regulation (EC) No. 1272/2008.