Methenamine

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1985

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 vivo mammalian bone marrow cytogenetic test (chromosomal analysis) - Result of testing UROTOVET(R).

Author:

Vujosevic, M., Zivkovic, S., Fister, S.

Year:

1986

Bibliographic source:

Acta Vet (Beograd), 36, 91-94

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

According to the method of Hsu and Patton (1969).

GLP compliance:

not specified

Type of assay:

mammalian bone marrow 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

Test animals

Species:

mouse

Strain:

C3H

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 10-12 weeks old
- Weight at study initiation: 20-25 g
- Animals were kept under standard conditions of temperature and relative humidity.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

distilled water

Details on exposure:

Test substance was administered per os (presumably gavage).

Duration of treatment / exposure:

Acute study: 3 different sampling times after single exposure: 6, 12 and 24 h.
Repeated dose study: 5 days

Frequency of treatment:

Acute study: single treatment
Repeated dose study: 5 exposures (24 h apart)

Post exposure period:

Acute study: 3 different sampling times after single exposure: 6, 12 and 24 h.
Repeated dose study: Sampling time was 6 h after last exposure

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 68.6, 205.9, 617.7mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

5 male animals per dose and time point

Control animals:

yes, concurrent vehicle

Positive control(s):

yes, Ethyl-methane sulfonate (EMS) was used at a concentration of 50 mg/kg bw.

Examinations

Tissues and cell types examined:

mice bone marrow cells

Details of tissue and slide preparation:

Chromosome preparations were made according to the method of Hsu and Patton (1969). Slides were stained in 10% Giemsa. At each experimental point 300 cells were scored (60 per animal).

Evaluation criteria:

The basic chromosomal abnormalities that were considered included chromatid and chromosome breaks and exchanges. For comparative purposes the basic index used was the number of breaks per metaphase (B/C).

Statistics:

not indicated.

Results and discussion

Test results

Key result

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

During the course of the experiment no animal died. No chromosome aberrations of the exchange type were observed in any of the test substance treated groups.

Applicant's summary and conclusion

Conclusions:

It can be concluded that under the testing conditions, the test substance concentrations used (high dose group 1/3 of LD50) did not show any mutagenic effect in cytogenetic analysis of mice bone marrow cells.

Executive summary:

Two in vivo chromosomal aberration tests in mice analysed bone marrow cells were negative. A negative result was obtained after single oral doses up to 618 mg/kg (corresponding to 1/3 of LD50-value) at sampling times of 6 h, 12 h, and 24 h after single treatments. In addition negative results after repeated oral doses were also determined. Doses up to 618 mg/kg bw were given five times with intervals of 24 h; sampling time was 6 h after last administration. No information about clinical symptoms or cytotoxic effects is given by the authors. However, from the toxicokinetic data available it can be concluded that the substance was available at the target organ (see section 7.1). Positive controls revealed the expected effects and demonstrated the sensitivity of the test system.