Methenamine

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991

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:

Genotoxicity of hexamethylenetetraamine.

Author:

Girmanova, I., Chalupa, I., Sekerka, V.

Year:

1991

Bibliographic source:

Biologia (Bratislava), 46, 11, 1009-1015

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Deviations:

not specified

Principles of method if other than guideline:

Sister chromatid exchange was measured additionally

GLP compliance:

not specified

Type of assay:

in vitro mammalian chromosome aberration test

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

Test material form:

solid: crystalline

Method

Target gene:

not applicable, chromosome aberration test

Species / strain

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

without

Test concentrations with justification for top dose:

0.1, 1, 10, 50 mmol/L

Vehicle / solvent:

water

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

mitomycin C

Details on test system and experimental conditions:

incubation time: 20 h (Chromosome aberration), 30 h (Sister chromatid exchanges)

Evaluation criteria:

100 metaphases from two replicates were evaluated.

Statistics:

Student t-test

Results and discussion

Test results

Key result

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

strong cytotoxic effect at a concentration of 50 mmol/L

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Chromosome aberrations:
In the highest analysable concentration of 10 mmol/l 7% aberrant cells (without gaps) were induced compared to 2% in control cultures. Higher doses were strongly cytotoxic.
Sister chromatid exchanges:
Slightly increased SCE frequencies were described after treatment of V79 cells with 10 and 50 mmol/l methenamine.
Historical control data and other critical parameters at high concentrations (osmolarity, pH) not reported.

Applicant's summary and conclusion

Conclusions:

Methenamine induced chromosome aberrations in the highest analysable concentration of 10 mmol/L. Slightly increased Sister Chromatid Exchange frequencies were also described after treatment of V79 cells with 10 and 50 mmol/L methenamine.

Executive summary:

In a mammalian cell cytogenetics assay (Chromosome aberration (CA) and Sister Chromatid Exchanges (SCE)), V79 cell cultures were exposed to methenamine in water at concentrations of 0, 0.1, 1, 10, 50 mmol/L without metabolic activation.

Methenamine was tested up to cytotoxic concentration. In the highest analysable concentration of 10 mmol/l 7% aberrant cells (without gaps) were induced compared to 2% in control cultures. Higher doses were strongly cytotoxic. Only one experiment without S-9 mix was done. In the same publication slightly increased SCE frequencies were described after treatment of V79 cells with 10 and 50 mmol/l methenamine. Positive controls induced the appropriate response. There was a concentration related positive response of Chromosome aberration and SCE induced over background.

This study is classified as acceptable but due to missing data about cytotoxicity a final evaluation is difficult. This study satisfies the requirement for Test Guideline (OECD 473, EU B.10 and in vitro sister chromatid exchange assay in V79 cells) for in vitro cytogenetic mutagenicity data.