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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1997-11-03 to 1998-07-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
GLP compliance:
yes
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Constituent 1
Reference substance name:
Polysulfides, di-tert-nonyl
EC Number:
270-336-2
EC Name:
Polysulfides, di-tert-nonyl
Cas Number:
68425-16-1
Molecular formula:
C78H110O6S5
IUPAC Name:
Polysulfides, di-tert-nonyl
Details on test material:
Test compound: TPS 37
Chemical name: di-t-nonyl polysulfide
CAS no.: 68425-16-1
Source: Elf Aquitaine Production
Batch: 47978
Sulfur content: 36.9%.

Method

Species / strain
Species / strain / cell type:
other: Human Lymphocytes
Metabolic activation:
with and without
Test concentrations with justification for top dose:
122.5, 175, 250 µg/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
DMF
Positive controls:
yes
Evaluation criteria:
The test article is considered as positive in this assay if:
1. a statistically significant increase in the proportion of cells with structural aberrations (excluding gaps) occurs at one or more concentrations, and
2. the proportion of cells with structural aberrations at such doses exceeds normal range

Results and discussion

Test results
Species / strain:
lymphocytes: human peripheral blood lymphocytes
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks on result:
no mutagenic potential (based on QSAR/QSPR prediction)

Any other information on results incl. tables

Experiment 1: treatment in the absence and presence of S-9

S-9           

Treatment + recovery (hours)

Vehicle Control

Concentration (µg/mL)

Positive Control

-

3 + 17

DMF

122.5, 175, 250         

NQO, 2.5.µg/mL

+

(Aroclor 1254 induced S-9)

3 + 17

DMF

122.5, 175, 250         

CPA, 25 µg/mL

Experiment 2: treatment in the absence of S-9

S-9           

Treatment + recovery (hours)

Vehicle Control

Concentration (µg/mL)

Positive Control

-

20 + 0

DMF

122.5, 175, 250         

NQO, 2.5.µg/mL

+

3 + 17

DMF

122.5, 175, 250         

CPA, 25 µg/mL

Applicant's summary and conclusion

Conclusions:
TPS 37 did not induce chromosome aberrations in cultured human peripheral blood lymphocytes when tested in excess of its limit of solubility in both the absence and presence of S-9.
Executive summary:

In a chromosome aberration study in mammals, human lymphocyte cultures from female donors were exposed to TPS 37 in 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 cell that were within the normal range. It is 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.

 

This study received a Klimisch score of 1 and is classified as reliable without restriction because it provides robust results and carefully follows OECD guidelines.