Tin disulphide

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The following in vitro tests for genetic toxicity have been performed on Tin disulfide with a negative result:
Ames test, Chromosomal Aberration test and gene mutation assay in mammalian cells
(Chinese Hamster ovary (CHO) cells).
These results were confirmed by in vitro studies and an in vivo study on the read-across substance tin sulfide.
The genotoxic potential of the read-across test item Tin sulfide (CAS 1314-95-0) was also demonstrated
to be negative in an Ames test, a Chromosomal Aberration test and a Micronucleus test (in vivo).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

The following in vivo tests for genetic toxicity have been performed on read-across substance tin sulfide

(CAS 1314-95-0) with a negative result: Micronucleus test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Ames test:

A key bacterial reverse mutation assay was performed with a suspension of Tin disulfide using TA98, TA100, TA1535 and TA1537 strains of S. typhimurium and WP2uvrA E. coli with and without metabolic activation (S9 fraction) prepared from Aroclor 1254 induced rat liver (Suresh, 2012). In a preliminary toxicity test, no cytotoxicity was seen up to 5000 µg/plate, with slight precipitation on the basal agar plates at 5000 µg/plate both with and without S9. Test doses were 50, 158, 500, 1580 and 5000 µg/plate using direct plate incorporation in the initial mutation assay and 100, 266, 707, 1880 and 5000 µg/plate using pre-incubation in the confirmatory assay. The results from the initial as well as from the confirmatory assays, indicate the tested doses showed no positive mutagenic increase in the mean numbers of revertant colonies for all tester strains when compared to the respective vehicle control plates, either with and without S9 up to the highest tested dose of 5000 µg/plate. A supporting study with read-across substance Tin sulfide using TA98, TA100, TA1535 and TA1537 strains of S. typhimurium and WP2uvrA E. coli with and without metabolic activation was also negative (Prochazkova, 2010). Tin disulfide and Tin sulfide showed a comparable toxicological profile for this endpoint.

 

Chromosome Aberration Test (in vitro):

A key study for chromosome aberrations was done with a suspension of Tin disulfide in cultured Chinese Hamster Ovary (CHO) cells, with and without metabolic activation (S9 fraction) prepared from Aroclor 1254 induced rat liver (Indrani, 2012). In a preliminary toxicity test, Tin disulfide showed evidence of significant growth inhibition at and above 229 µg/mL and 457 µg/mL during 3 hour exposure with and without S9, respectively, whereas in the absence of S9 with 21-hour exposure, there was evidence of significant reduction in the growth of CHO cells at and above 229 µg/mL. Exposure of Tin disulfide did not cause any appreciable change in the pH and osmolality of test solutions. In the definitive chromosome aberration assay, CHO cells were exposed to the test item in duplicate at concentrations of 23, 73 and 230 µg/mL (3 hours + S9 and 21 hours - S9) and at 30, 95 and 300 µg/mL (3 hours -S9). At the highest concentration tested at 3 hours (230 and 300 µg/mL), the reduction in the cell growth was 51% and 52% with and without S9, respectively, whereas at 21 hours without S9 (230 µg/mL), the reduction in cell growth was 53% when compared to the sterile water control. A total of 200 metaphases per dose level from duplicate cultures from the sterile water control, each treatment group and the positive control were evaluate for chromosome aberrations. There was no evidence of induction of chromosome aberrations, including or excluding gaps, either in the presence or in the absence of metabolic activation in any of these experiments. In each of these experiments, under identical conditions, the respective positive control substances produced a large and statistically significant increase in aberrant metaphases. As a supporting study, the clastogenicity potential of Tin sulfide was determined using In Vitro Chromosome Aberration Test (Kovarik, 2010). The test was carried out in human peripheral blood lymphocytes with and without metabolic activation system in two separate assays. Tin sulfide did not induce an increase in numerical and structural chromosome aberrations in cultured peripheral blood lymphocytes. Further, an in vivo micronucleus test according to OECD TG 474 was performed with Tin sulfide, also demonstrating absence of micronuclei in the immature erythrocytes in the bone marrow (Prochazkova, 2010). Tin disulfide and Tin sulfide showed a comparable toxicological profile for this endpoint.

 

Mammalian gene mutation Test (in vitro):

A key gene mammalian mutation assay with Tin disulfide was conducted in Chinese Hamster ovary (CHO) cells in the presence and absence of metabolic activation system (S9 fraction) prepared from Aroclor 1254 induced rat liver (Bopanna, 2012). In a preliminary cytotoxicity test Tin disulfide did not cause a significant cell growth inhibition as evaluated by Relative Cloning efficiency (RCE) up to the highest tested concentration of 1828.42 µg/mL (equivalent to 10 mM) with and without S9. The test item formed precipitation of the test solution at and above 7 µg/mL but did not cause any appreciable change in the pH and osmolality of the test solutions at the end of the 3-hour exposure to treatment either in the presence or in the absence of metabolic activation. In the initial gene mutation assay, CHO cells were exposed at 58, 183, 578 and 1828 µg/mL for 3 hours with and without S9; in the confirmatory gene mutation assay concentrations of 68, 203, 609 and 1828 µg/mL were applied for 3 hours with and without S9. There was no evidence of induction of gene mutations in any of the test material treated cultures either in the presence or absence of metabolic activation. The results of the forward gene mutation assay at the hprtlocus with Tin disulfide indicate that under the conditions of this study, the test item was non-mutagenic when evaluated in the presence or absence of S9 system.

 

Mammalian Erythrocyte Micronucleus Test (in vivo):

The potential of read-across substance Tin sulfide to cause cytogenetic damage was assessed in a Mammalian Erythrocyte Micronucleus Test according to OECD guideline 474.
No changes in health status and condition of the animals in any of the groups were recorded during the acclimation and during the study. No significant changes of mean body weight were observed in the animals during the study. All the values of number of NPCE in all dose groups were within the reference range for negative control group. No statistically significant higher values of number of NPCE in any of the dose groups (up to 11 of micronuclei) as compared to negative control group (up to 13 of micronuclei) were noted. Statistically significant differences were observed in the positive control group (NPCE – up to 38 of micronuclei) as compared to control group.
Read-across substance Tin sulfide does not induce damage to the chromosomes or the mitotic apparatus of erythroblasts.

 

Short description of key information: Key studies for bacterial and mammalian mutagenicity and chromosome aberrations were performed for Tin disulfide, all demonstrating absence of genotoxic potential. In addition, supporting studies for read-across substance Tin sulfide also showed absence of mutagenicity and chromosome aberration in a bacterial reverse mutation and in vitro chromosome aberration and in vivo Micronucleus assay. 

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

No classification and labelling is needed for genotoxicity (bacterial and mammalian mutations; chromosome aberrations) for Tin disulfide according to EU labelling regulations Commission Directive 93/21/EEC and CLP regulation (No. 1272/2008 of 16 December 2008).