2,3-bis((2-mercaptoethyl)thio)-1-propanethiol

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Bacterial reverse mutation assay (OECD 471): negative with and without metabolic activation Mammalian chromosome aberration test, human lymphocytes (OECD 473): negative with and without metabolic activation

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Assessed after consultation with the relevant Authority. Data migrated from NONS (67/548/EEC notification) files provided by Authority contained insufficient information.

Qualifier:

according to guideline

Guideline:

other: OECD 471 and 472

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

GLP compliance:

yes

Remarks:

No further information was provided in the SNIF file.

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

bacteria, other: S. typhimurium TA98, TA100, TA1535, TA1537, and E. coli WP2 uvrA

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

S9-mix

Test concentrations with justification for top dose:

Concentration range in the main test (with metabolic activation): 50-5000 ¿g/plate.
Concentration range in the main test (without metabolic activation): 50-5000 ¿g/plate.

Vehicle / solvent:

Solvent: DMSO

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

not specified

Positive control substance:

not specified

Species / strain:

other: as specified above

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

5000 µg/plate

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

Observations: no increase in the number of revertant colonies.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'. Remarks: preliminary test and main test

Conclusions:

Interpretation of results (migrated information):
negative

According to DSD 67/548/EEC, the substance is not classified as mutagenic.
According to Regulation (EC) No 1272/2008, the substance is not classified as mutagenic.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

There are three in vitro studies available. These studies assesses the mutagenicity of 2,3 -bis(2 -mercaptoethyl)thio)-1 -propanethiol in bacteria, clastogenicity in a mammalian cell line and mutagenicity in a human cell line.

 

The mutagenic effect in bacteria was investigated in a bacterial reverse mutation assay (Ames test) with 5 standard strains (Mitsui 1993, SNIF#001 -4.3.10 -01). In this study the Salmonella typhimurium TA98, TA100, TA1535 and TA1537, and Eschericia coli WP2 uvrA strains were exposed to the test substance with or without metabolic activation (S9 -mix). The concentration range was 50 - 5000 µg/plate both and without metabolic activation. Cytotoxic effects were observed at 5000 µg/plate with and without S9 -mix. Under the conditions of the study the test substance did not induce gene mutations.

 

An in vitro chromosome aberration test (Mitsui 1993, SNIF#001-4.3.28 -01) was performed in human lymphocytes to assess the clastogenic potential of 2,3 -bis((2 -mercaptoethyl)thio)-1-propanethiol in mammalian cells. The cells were exposed to concentrations in the range 20 - 80 µg/mL for 3 hours with metabolic activation (S9 -mix), and in the range 10 - 40 µg/mL for 3, 24 and 48 hours without metabolic activation. Cytotoxicity was observed at concentrations >40 µg/mL and > 10 µg/mL with and without S9 -mix, respectively. Under the conditions of the study, 2,3 -bis((2 -mercaptoethyl)thio)-1 -propanethiol did not induce biologically significant chromosomal aberrations in the human lymphocytes, and therefore the substance is not clastogenic.

Justification for selection of genetic toxicity endpoint
Key study. Ames study was selected, however other genotoxic endpoints are equially valuable.