1-(2-hydroxyethyl)-1H-pyrazol-4,5-diyldiammoniumsulfate

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: Guideline study under GLP conditions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1-(2-hydroxyethyl)-1H-pyrazol-4,5-diyldiammoniumsulfate

EC Number:

429-300-3

EC Name:

1-(2-hydroxyethyl)-1H-pyrazol-4,5-diyldiammoniumsulfate

Cas Number:

155601-30-2

Molecular formula:

C5H12N4O5S

IUPAC Name:

2-(4,5-diamino-1H-pyrazol-1-yl)ethan-1-ol; sulfuric acid

Details on test material:

Batch GSF 4-20079

Method

Target gene:

TA1537: his C3076; da-; uvrß- frame shift mutations
TA1538: his ; da-; uvrß- frame shift mutations
TA 98: his D 3052; rfa-; uvrß-; R-factor frame shift mutations
TA1535: his G 46; rfa-; uvrß- base-pair substitutions
TA 100; his G 46 ; rfs-, uvrß- base-pari substitutions

Species / strain

Species / strain 1

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not specified

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1538

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

S9-homogenate

Test concentrations with justification for top dose:

1µg, 10µg, 100µg, 1000µg and 5000µg

Vehicle / solvent:

Water

Controls

Controls 1

Untreated negative controls:

yes

Remarks:

Water

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

fro TA 1535 and TA 100

Controls 2

Untreated negative controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

for TA 1537

Controls 3

Untreated negative controls:

yes

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

TA 1538 and TA 98

Evaluation criteria:

A test substance is considered mutagenic if there is a reproducibly increasing dose-response curve of induced colonies for at least three concentrations. The minimal criteria for a positive response are two- to threefold increase in the number of revertants (at least 10 colonies) over the sponaneous number for the stains TA 1535, TA 1537, TA 1538 and TA 98, and a 50% increase for TA 100. Less pronounced effects without dose-resposne releationship are reported as equivocal results (+_)in the table of results (summary) and are considered to be biologically not relevant. More over, to avoid a misinterpretation of the mutagenicity data, the positive response should not be obtained only at concentratons near to toxic dose levels.

Results and discussion

Test results

Test results 1

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

The test substance Pyrazole DHE has no mutagenicity potential in concentration till 5000µg per plate in the testes species

Executive summary:

The study was perfomed to investigate the potential of Pyrazole DHE to induce gene mutations according to the OECD Guideline 471.

The strains were exposed on minimal agar platesto a range of concentrationsof the test substance (up to 5000µg/ plate) both in the presents and absence of an exogenous metabolic activation system. The testet strain were TA 1535, TA 1538, TA 1538, Ta 98, and TA 100.

Results:

The mean numbers of spontaneous revertant colonies on untreated and /or solvent treated plates (= negative controls values or background revertant counts) are within the normal range previously esthablished in our laboratory and agree with the values from the literature. Similary, the results with the positive control substances confrim the sensitivity of the tester strains as well as the activity of the metabolizing system.

In this Ames reversion the test substance "DA 010894" (Pyrazole DHE) did not induce any significant increase in the number of revertant colonies on the plates, with any of the bacterial tester strains used, either in the presents or absence of S9 -mix, at concentratons ranging from 1 to 5000 µg per plate.

Some groth inhibiting or toxic effects, detected as significant decreases in the number of spontaneous revertants per plate and/or presence of a sparse bacterial background lawn were observed with TA 1537 and TA 98, without S9 -mix, and TA 100 with S9 -mix, at the highest dose leves of 3000/5000µg per plate.

Therefore it can be concluded that the Test Substance "DA 010894" (Pyrazole DHE was not mutagenic in the Ames reversion assay!