Methanesulfonic acid, 1,1'-(1,6-hexanediyldiimino)bis[1-oxo-, sodium salt (1:2)

Genetic toxicity: in vitro

Administrative data

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

Isotan LP RJE 69140 was initially investigated using the Salmonella/microsome plate incorporation test for point mutagenic effects in doses of up to and including 5000 µg per plate on five Salmonella typhimurium L T2 mutants. These comprised the histidine- auxotrophic strains TA 1535, TA 100, TA 1537, TA 98 and TA 102. The independent repeat was performed as preincubation for 20 minutes at 37°C.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Methansulfonic acid (1,6-hexanediyl-diimino)bis[1-oxo, disodium salt

EC Number:

690-526-2

Cas Number:

38632-47-2

Molecular formula:

C8H14S2N2O8.Na2

IUPAC Name:

Methansulfonic acid (1,6-hexanediyl-diimino)bis[1-oxo, disodium salt

Details on test material:

composition: 31.94% hexamethylenediisocyanate-bisulfite-adduct, 2.27% emulsifier, 0.79% citric acid monohydrate, 65.00% water

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Additional strain / cell type characteristics:

other: partly deficient in lipopolysaccharide side chains in their cell walls and with the exception of TA 102 all strains have reduced capability to repair DNA-damage

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix

Test concentrations with justification for top dose:

0, 50, 158, 500, 1581, 5000 µg per plate or tube

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: The positive controls sodium azide, nitrofurantoin" 4-nitro-1,2-phenylene diamine, mitomycin C and cumene hydroperoxide were only used without 59 mix; the positive control 2-aminoanthracene was only used with S9 mix.

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: Doses up to and including 500 JJg per plate did not cause any bacteriotoxic effects.

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: other: S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Doses up to and including 500 µg per plate did not cause any bacteriotoxic effects. Total bacteria counts remained unchanged and no inhibition of growth was observed.

At higher doses, the substance had a strain-specific bacteriotoxic effect. Due to this effect this range could nevertheless be used, however, partly only to a limited extent up to 5000 µg per plate for assessment purposes.

Evidence of mutagenic activity of Isotan LP RJE 69140 was not seen. No biologically relevant increase in the mutant count, in comparison with the negative controls, was observed.

The positive controls sodium azide, nitrofurantoin, 4-nitro-1,2-phenylene diamine, mitomycin C, cumene hydroperoxide and 2-aminoa,nthracene had a marked mutagenic effect, as was seen by a biologically relevant increase in mutant colonies compared

to the corresponding negative controls.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Executive summary:

Isotan LP RJE 69140 was initially investigated using the Salmonella/microsome plate incorporation test for point mutagenic effects in doses of up to and including 5000 µg per plate on five Salmonella typhimurium L T2 mutants. These comprised the histidine- auxotrophic strains TA 1535, TA 100, TA 1537, TA 98 and TA 102. The independent repeat was performed as preincubation for 20 minutes at 37°C.

Doses up to and including 500 µg per plate did not cause any bacteriotoxic effects. Total bacteria counts remained unchanged and no inhibition of growth was observed.

At higher doses, the substance had a strain-specific bacteriotoxic effect. Due to this effect this range could nevertheless be used, however, partly only to a limited extent up to 5000 µg per plate for assessment purposes.

Evidence of mutagenic activity of Isotan LP RJE 69140 was not seen. No biologically relevant increase in the mutant count, in comparison with the negative controls, was observed.

The positive controls sodium azide, nitrofurantoin, 4-nitro-1,2-phenylene diamine, mitomycin C, cumene hydroperoxide and 2-aminoa,nthracene had a marked mutagenic effect, as was seen by a biologically relevant increase in mutant colonies compared

to the corresponding negative controls.

Therefore, Isotan LP RJE 69140 was considered to be negative without and with 59 mix in the plate incorporation as weil as in the preincubation modification of the Salmonella/microsome test (Ames test).