Tin(2+) neodecanoate

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

Study period:

14-11-2017 to 24-01-2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Tin(2+) neodecanoate

EC Number:

256-370-0

EC Name:

Tin(2+) neodecanoate

Cas Number:

49556-16-3

Molecular formula:

C20H38O4Sn

IUPAC Name:

λ²-tin(2+) bis(2,2-dimethyloctanoate)

Test material form:

liquid

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:

S9 mix (rat; Arochlor 1254 induced)

Test concentrations with justification for top dose:

10.0, 31.6, 100, 316, 1000 and 3160 µg / plate

Vehicle / solvent:

acetone

As the test substance dissociates in water an organic solvent was used. For the experiment the solvent acetone was chosen.

Controls

Controls 1

Untreated negative controls:

other: acetone

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

without metabolic activation: TA 1535; TA 100; 10 µg/plate

Controls 2

Untreated negative controls:

other: acetone

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

without metabolic activation: TA 1537; 100 µg/plate

Controls 3

Untreated negative controls:

other: acetone

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

without metabolic activation: TA 98, 10 µg/plate

Controls 4

Untreated negative controls:

other: acetone

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

mitomycin C

Remarks:

without metabolic activation: TA 102, 10 µg/plate

Controls 5

Untreated negative controls:

other: acetone

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

with metabolic activation: TA100, TA1535, 2 µg/plate

Controls 6

Untreated negative controls:

other: acetone

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Remarks:

with metabolic activation: TA 98, TA 102, TA 1537, 10 µg/plate

Details on test system and experimental conditions:

The first experiment was carried out as the standard plate incorporation method whereas the second was carried out as the preincubation method.

Evaluation criteria:

A test substance producing no biologically relevant positive response in any one of the bacterial strains tested is considered to be non-mutagenic in this system.
A biologically relevant response is described as follows:
If the number of revertants is at least twice the spontaneous reversion rate for TA 1535, TA 98, TA 100 or TA 1537 (and 1,5-fold for TA 102) and/or if there is a concentration related increasing number of revertants over the range tested.

Statistics:

yes, p <= 0.05, U-test according to MANN and WHITNEY

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 5

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Water solubility: The test substance dissociates in water, therefore an organic solvent was used.
- Precipitation: test item precipitation was noted at concentrations of 3160 and 5000 µg / plate in both experiments.


COMPARISON WITH HISTORICAL CONTROL DATA: The results of the negative and positive control cultures were within the range of the historical data generated by LPT

ADDITIONAL INFORMATION ON CYTOTOXICITY:
Complete cytotoxicity (scarce background lawn and reduction of the number of revertants by more than 50%) was noted starting at a concentration of 3160 µg PU-2017-763/plate in both experiments.

Applicant's summary and conclusion

Conclusions:

Interpretation of results:
negative

The reported data show that the test item neodecanoic acid tin (2+)salt (2:1) did not induce gene mutations in the S. typhimurium tester strains with and without mammalian metabolic activation. In conclusion the results of this bacterial reverse mutation assay were considered negative.

Executive summary:

The potential of Neodecanoic acid, tin(2+) salt (2:1) to induce gene mutations was examined in 5 Salmonella typhimurium strains TA98, TA100, TA102, TA1535 and TA1537 in two independent experiments, each carried out without and with metabolic activation (a microsomal preparation derived from Aroclor 1254-induced rat liver). The first experiment was carried out as a plate incorporation test and the second as a preincubation test.

Six concentrations ranging from 10.0 to 3160 μg Neodecanoic acid, tin(2+) salt (2:1)/plate were employed in the plate incorporation test and in the preincubation test, each carried out without and with metabolic activation.

Pronounced cytotoxicity (scarce background lawn and reduction of the number of revertants) was noted in the plate incorporation test and in the preincubation test, each carried out without and with metabolic activation at the top concentration of 3160 μg Neodecanoic acid, tin(2+) salt (2:1)/plate in all test strains. In addtion, test item precipitation was noted at the top concentration of 3160 μg Neodecanoic acid, tin(2+) salt (2:1)/plate in both experiments in all test strains.

No increase in revertant colony numbers as compared with control counts was observed for Neodecanoic acid, tin(2+) salt (2:1), tested up to a concentration that led to cytotoxicity and test item precipitation, in any of the 5 test strains in two independent experiments without and with metabolic activation, respectively (plate incorporation test and preincubation test).

The positive control items showed a significant increase in the number of revertant colonies of the respective test strain and confirmed the validity of the test conditions and the sensitivity of the test system.

In conclusion, under the present test conditions, Neodecanoic acid, tin(2+) salt (2:1) tested up to a concentration that led to cytotoxicity and test item precipitation caused no mutagenic effect in the Salmonella typhimurium strains TA98, TA100, TA102, TA1535 and TA1537 neither in the plate incorporation test nor in the preincubation test each carried out without and with metabolic activation.