Methenamine

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

Study period:

1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: public available literature (non GLP, no guideline)

Data source

Reference

Reference Type:

publication

Title:

In vitro mutagenicity of rubber chemicals and their nitrosation products.

Author:

Crebelli, R., Falcone, E., Aquilina, G., Carere, A.

Year:

1984

Bibliographic source:

Toxicol. Lett. 23, 307-313

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

not specified

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Methenamine

EC Number:

202-905-8

EC Name:

Methenamine

Cas Number:

100-97-0

Molecular formula:

C6H12N4

IUPAC Name:

1,3,5,7-tetraazatricyclo[3.3.1.1³,⁷]decane

Details on test material:

technical grade (employed in a tyre plant)

Method

Target gene:

histidine operon.

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA98 and TA100

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

S 9 mix

Test concentrations with justification for top dose:

0, 200, 1000, 5000 µg/plate

Vehicle / solvent:

water

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

other: 1342 4-nitro-ophenylenediamine

Remarks:

TA98 without S9 mix

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

other: 1342 2-aminoanthracene

Remarks:

TA98 and TA100 with S9 mix

Details on test system and experimental conditions:

preincubation method.

Evaluation criteria:

2-fold increase of revertants compared to negative control.

Statistics:

standard deviation

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA98 and TA100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

None

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Methenamine is not mutagenic in Ames test up to limit concentration of 5000 µg/plate.

Executive summary:

In a reverse gene mutation assay in bacteria, strains TA98 and TA100 of S. typhimurium were exposed to methenamine in water at concentrations of 0, 200, 1000, 5000 µg/plate in the presence and absence of mammalian metabolic activation (S9 mix). Methenamine was tested up to the limit concentration of 5000 µg/plate.

The positive controls induced the appropriate responses in the corresponding strains. There was no evidence of induced mutant colonies over background at any test concentration with methenamine. Consequently, methenamine is evaluated to be not mutagenic in the Ames test if tested up to the limit concentration of 5000 µg/plate.

This study is classified as acceptable. This study was conducted under equivalent or similar conditions compared to the requirements of EU Method B.13/14 and OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) data.