Bis(dodecylthio)dimethylstannane

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Read-across to structurally similar substance DMTE (Dimethyltin bis (2-ethylhexyl thioglycolate) CAS 57583-35-4)

In vitro gene mutation (reverse mutation assay, Ames): S. typhimurium and E. coli- negative in all strains with and without metabolic activation.

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not specified

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Restriction: Composition/purity of the test material not reported.

Reason / purpose for cross-reference:

other: read-across target

Qualifier:

according to guideline

Guideline:

other: OECD, USEPA and USFDA and proposed revisions to OECD (1994). Specific guidelines not provided.

Deviations:

yes

Remarks:

analyses were not performed to verify the homogeneity, stability or accuracy of preparation of the test and control article dosing solutions.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Target gene:

Strains TA1535 and TA100 detect base pair substitution mutations affecting the hisG46 allele.
Strain TA98 detects frameshift mutations affecting the hisD3052.
Strain TA1537 detects frameshift mutations affecting the hisC3076 allele.
Strain TA102 can detect a variety of genetic damage affecting AT base pairs in the hisG428 allele.
Strain WP2 uvrA detects AT base pair mutations at the trp locus.

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain / cell type:

S. typhimurium TA 102

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced male Sprague-Dawley rat liver homogenate

Test concentrations with justification for top dose:

16.7, 50, 167, 500, 1670, and 5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: the test material demonstrated solubility in the solvent.

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Evaluated in the absence of S9: sodium azide; 9-aminoacridine; 2-nitrofluorene; mitomycin C; ENNG. In the presence of S9: 2-aminofluorene and 2-anthramine

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium; in agar (plate incorporation) and pre-incubation.
Evaluated in both toxicity pre-screen and mutation assays using both the liquid pre-incubation and plate incorporation treatment.

DURATION
- Preincubation period: 30 minutes (liquid pre-incubation method)
- Exposure duration: 48 hours
- Expression time (cells in growth medium): 48 hours
- Selection time (if incubation with a selection agent): 30 minutes
- Fixation time (start of exposure up to fixation or harvest of cells): 48 hours

SELECTION AGENT: Na2HPO4

NUMBER OF REPLICATIONS: triplicate

Evaluation criteria:

A positive result is defined as a statistically significant, dose-dependent increase in the number of histidine- or tryptophan-independent revertants with at least one dose level inducing a revertant frequency that is two-fold the solvent control value. If the test material does not induce a statistically significant, dose-dependent increase in revertant frequency, but does induce a revertant frequency at one dose level that is two-fold the spontaneous control value, the result is considered equivocal. A negative result is defined as the absence of a statistically significant or dose-dependent increase in the number of histidine or tryptophan-independent revertants.

Statistics:

Statistical analyses were conducted using the program developed by Snee and Irr (1981), with significance established at the 95% confidence limit.

Key result

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

Primary test results revealed that in the liquid pre-incubation assay, growth was inhibited in strains TA1535, TA1537, and TA100 at ≥ 500 µg/plate (in the presence and absence of metabolic activation. Toxicity to strain TA98 was reported at ≥ 1670 µg/plate (without activation) and ≥ 500 µg/plate (with activation). Growth was inhibited in strain TA102 at ≥ 1670 µg/plate (both with and without activation). A dose level of 5000 µg/plate inhibited growth of strain WP2 uvrA without metabolic activation, and ≥ 1670 µg/plate with metabolic activation. In the plate incorporation assay, both with and without metabolic activation, growth was inhibited in strain TA1537 at ≥ 500 µg/plate and in strain TA1535 at 5000 µg/plate. In the presence of S9, growth in TA100 and TA102 was inhibited at 5000 µg/plate, and without S9 at ≥ 1670 µg/plate. A dose level of ≥ 500 µg/plate inhibited growth in TA98 (without S9) and at ≥ 1670 µg/plate (with S9). No growth inhibition was observed in WP2 uvra. Again, the test material was reported to be incompletely soluble at levels ≥ 500 µg/plate.

RANGE-FINDING/SCREENING STUDIES: Preliminary test results revealed that the test material produced inhibited growth in both Salmonella tester strains (TA1537 and TA100) at doses ≥ 500 µg/plate, under liquid pre-incubation conditions. Additionally, the test material was found to be incompletely soluble at levels ≥ 500 µg/plate.

COMPARISON WITH HISTORICAL CONTROL DATA: all positive and negative control values in both assays were within acceptable historical ranges.

Conclusions:

The results of the tests conducted on the test material, for both liquid pre-incubation and plate incorporation treatments, in the presence and absence of a metabolic activation system, were negative at dose levels below the solubility of the test material.

Executive summary:

The test material was evaluated in the Ames/Salmonella-E. coli Reverse Mutation Assay to determine its ability to induce reverse mutations at selected histidine loci in five tester strains of Salmonella typhimurium (TA1535, TA1537, TA100, TA98, TA102) and at the tryptophan locus in one Escherichia coli tester strain (WP2 uvrA), in both the presence and absence of an exogenous metabolic activation system (S9).

Toxicity of the test material was first evaluated in a preliminary toxicity screen using both liquid pre-incubation and plate incorporation treatment conditions. Duplicate cultures were treated at doses of 50.0, 167, 500, 1670 and 5000 µg/plate, and the DMSO solvent control, in the absence of S9. Results of the pre-screen indicated that the test material produced inhibited growth in both Salmonella tester strains at doses ≥ 500 µg/plate under liquid pre-incubation conditions. In addition, the test material was found to be incompletely soluble at doses ≥ 500 µg/plate.

The test material next was evaluated for mutagenicity using both treatment conditions. Based upon the results of the pre-screen, the test material was evaluated in triplicate cultures in all six tester strains at doses of 16.7, 50.0, 167, 500, 1670 and 5000 µg/plate with and without S9. Six doses of the test material were evaluated in the event of unacceptable toxicity and/or insolubility at the highest dose levels evaluated in the mutation assay. The S9 mixture included 6 % (v/v) Aroclor 1254-induced male Sprague-Dawley rat liver homogenate with the appropriate buffer and cofactors. Except for strain WP2 uvrA under plate incorporation conditions, inhibited growth again was observed for all strains/S9/treatment combinations at the highest 1-3 doses evaluated. In addition, the test material again was found to be incompletely soluble at doses ≥ 500 µg/plate. Revertant frequencies for all doses of the test material in all tester strains with and without S9, under both treatment conditions, approximated or were less than those observed in the concurrent negative control cultures. All positive and negative control values in both assays were within acceptable ranges.

Therefore, the results for the test material were negative in the Ames/Salmonella-E. coli Reverse Mutation Assay, using liquid pre-incubation and plate incorporation treatments, under the test conditions.

Reference 2

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted on read-across material

Justification for type of information:

Read-across to structurally similar substance DMTE (Dimethyltin bis (2-ethylhexyl thioglycolate) CAS 57583-35-4), see attached justification.

Reason / purpose for cross-reference:

read-across source

Key result

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Read-across to structurally similar substance DMTE (Dimethyltin bis (2-ethylhexyl thioglycolate) CAS 57583 -35 -4)

Data from an OECD 471 equivalent study are used to address gene mutation in bacterial cells. Salmonella typhimurium strains TA1537, TA1535, TA98, TA100 and TA102 and Escherichia coli strain WP2 uvrA were tested in the presence and absence of metabolic activation. The test material was evaluated using both the liquid pre-incubation and plate incorporation treatment methods. Revertant frequencies for all doses in all strains with and without activation, under both treatment conditions, approximated or were less than those observed in the concurrent negative control cultures. The result for the test material is negative.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to genetic toxicity.