Tin, dioctylbis(2,4-pentanedionato-.kappa.O2,.kappa.O4)-

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in mammalian cells

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Sep 2010 - Feb 2011

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Deviations:

no

GLP compliance:

yes

Type of assay:

mammalian cell gene mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

483-270-6

EC Name:

-

Cas Number:

54068-28-9

Molecular formula:

Hill formula: C26H48O4Sn CAS formula: C26H48O4Sn

IUPAC Name:

(3Z)-4-{[dioctyl({[(2Z)-4-oxopent-2-en-2-yl]oxy})stannyl]oxy}pent-3-en-2-one

Details on test material:

TIB KAT 223 VP10-054

Method

Target gene:

HPRT (hypoxanthine-guanine phosphoribosyl transferase)

Species / strain

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

S9-mix

Test concentrations with justification for top dose:

The concentrations evaluated (in bold) in the different experiments were:
4-hour first experiment:
without S9-mix: 100p, 50p, 25p, 12.5p, 6.25, 3.13, 1.56, 0.78, 0.39 and
0.2 μg/mL.
with S9-mix: 100p, 50p, 25, 12.5, 6.25, 3.13, 1.56, 0.78, 0.39 and
0.2 μg/mL.
6-hour second experiment:
without S9-mix: 25p, 12.5p, 6.25, 3.13, 1.56, 0.78, 0.39 and 0.2 μg/mL.
with S9-mix: 50p, 25p, 12.5, 6.25, 3.13, 1.56, 0.78 and 0.39 μg/mL.
p precipitation
In all cases, the highest concentration in the culture medium did not change the osmolality of
more than 50 mOsm/kg and did not change the pH value of more than 1.0 unit compared to the
concurrent negative control

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

other: Ethyl methanesulfonate (-S9); 7,12-dimethylbenz[a]anthracene (+S9)

Results and discussion

Test results

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

other: not mutagen

Cytotoxicity / choice of top concentrations:

other: not mutagen

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'.

Any other information on results incl. tables

The purpose of this study was to evaluate the potential of TIB KAT 223 to induce forward mutation at the HPRT (hypoxanthine-guanine phosphoribosyl transferase) locus in V79 Chinese Hamster lung cells with and without metabolic activation by liver homogenate (supplemented with cofactors and salts, ie, S9-mix) obtained from rats pretreated with Aroclor. TIB KAT 223 was suspended and diluted in cell culture medium. Depending on the experiment, cells were exposed to TIB KAT 223 for 4 or 6 hours with and without S9-mix. At the end of the exposure period the cloning efficiency was evaluated in microtiter plates. After a phenotypic expression period of 3 to 4 days, cells were cloned for 7 days in 75 cm2 flasks containing the selection agent 6-thioguanine (TG) for the determination of mutant frequency and in nonselective medium to measure the cloning efficiency. In addition, the number of the mutant colonies was determined. In a solubility pre-test concentrations from 0.01 to 5 mg/mL were investigated using the unaided eye for solubility, homogeneity and precipitation evaluation of the test compound in cell culture medium. In this pre-test all concentrations (except 0.01 mg/mL) were found to be suspensions. However, at 0.1 mg/mL (100 μg/mL) we observed a homogenous distribution of the particles. Therefore, 100 μg/mL was chosen as top treatment concentration in accordance to the OECD 476 Guidline. The highest evaluated concentrations were limited by test article precipitation observed at 12.5 μg/mL and above without S9 mix and 50 μg/mL (Exp. 1) respectively 25 μg/mL (Exp. 2) and above with S9 mix.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

In conclusion, under the experimental conditions of the study, TIB KAT 223 was found negative
in the mutation assay with V79 Chinese Hamster cells at the HPRT (hypoxanthine-guanine
phosphoribosyl transferase) locus in the presence or absence of metabolic activation up to
concentrations exhibiting test article precipitation