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In Vitro Genetic Toxicity

 

In Vitro Gene Mutation in Bacteria:

 

One key study was identified to evaluate the in vitro gene mutation potential of di-tert-nonyl polysulfide in bacteria.

 

In a key reverse gene mutation assay in bacteria (Dawkes, 1998; Klimisch score = 1), strains TA98, TA100, TA1535, TA1537 and TA102 of S. typhimurium were exposed to TPS 37 in DMF at concentrations of 8, 40, 200, 1000, and 5000 µg/plate in the presence and absence of mammalian metabolic activation using the Ames test.TPS 37 was tested up to limit concentrations of 5000 µg/plate. Following treatment in experiment 1, evidence of toxicity was observed at the highest dose (5000 µg/plate) tested in a few test strains of S. typhimurium. Precipitation of the test material was observed on all plates at concentrations of 1000 and 5000 µg/plate. For experiment 2, dose intervals were narrowed to more closely investigate concentrations of TPS 37 most likely to induce mutagenic response. All treatments in the presence of S-9 employed a pre-incubation step. Evidence of toxicity was found in the higher test doses in the presence and absence of S-9 mix. Precipitation of test agent was observed on all plates at concentrations of 1250 and 5000 µg/plate.

Treatment with TPS 37 did not produce an increase in revertant numbers high enough to be considered characteristic of mutagenic activity in any of the strains tested. Under the conditions of this study, TPS 37 did not induce mutation in five strains of S. typhimurium in the presence or absence of metabolic activation and was therefore considered to be negative in the bacterial reverse mutation test. 

In Vitro Cytogenicity in Mammalian Cells:

One key study was identified to evaluate the in vitro cytogenicity potential of di-tert-nonyl polysulfide in mammalian cells.

In a key chromosome aberration study (Burman, 1998; Klimisch score = 1), human lymphocyte cultures from female donors were exposed to TPS 37 in dimethyl formamide (DMF) at concentrations of 122.5, 175, and 250 µg/mL in the presence and absence of mammalian metabolic activation (S-9 mix) for up to 20 hours.TPS 37 was tested up to concentrations of 250 µg/mL. Cultures treated with TPS 37 in the absence and presence of S-9 exhibited frequencies of cells with structural aberrations which were similar to levels seen in concurrent negative controls. One culture treated with 122.5 µg/mL for 20 hours in the absence of S-9 displayed frequencies of cells with structural aberrations that exceeded the normal range for negative controls. A replication did not produce similar results so the effect was not considered biologically relevant. All other tests exhibited frequencies of cells that were within the normal range. It was therefore concluded that TPS 37 did not induce chromosome aberrations in cultured human peripheral blood lymphocytes when tested in the presence and absence of S-9 mix. 

In Vitro Gene Mutation in Mammalian Cells:

No key data were identified to evaluate the in vitro gene mutation potential of di-tert-nonyl polysulfide in mammalian cells. However, in vitro studies are planned for structural analogues di-tert-butyl polysulfide and di-tert-dodecyl polysulfide and results will be included once those study reports are made available.

In Vivo Genetic Toxicity:

No key data were identified to evaluate the in vivo genetic toxicity potential of di-tert-nonyl polysulfide or any of its structural analogues. A data waiver or data gap statement will be included once the results of the in vitro gene mutation tests (discussed earlier) are made available. 


Justification for selection of genetic toxicity endpoint
Based on in-vitro mutation and cytogenetic data available currently.

Short description of key information:
In-vitro mutation and cytogenetic data available show no effects - see discussion. Further studies to investigate in-vitro gene mutation effects in mammalian cells for structurally related analogues are planned.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Currently available in-vitro mutation and cytogenetic data data do not meet the criteria for classification under EU CLP Regulation 1272/2008.

Classification for this endpoint to be reviewed once data from the in vitro gene mutation studies are available.