Methenamine

Repeated dose toxicity: other routes

Administrative data

Endpoint:

sub-chronic toxicity: other route

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1961

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: old public available literature (non GLP, non guideline). Route of exposure and dose regime not relevant.

Data source

Reference

Reference Type:

publication

Title:

Untersuchungen an Ratten zur Verträglichkeit von Hexamethylentetramin.

Author:

Brendel, R.

Year:

1964

Bibliographic source:

Arzneimittel-Forsch. 14, 51-53

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Public available literature. No guideline indicated. For details on method see IUCLID5 materials and methods section.

GLP compliance:

not specified

Limit test:

yes

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:

rat

Strain:

other: BD II (cPah)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Forschung. und Untersuchungsinstitut für Milchvitaminierung, Frankfurt am main, Germany
- Age at study initiation: 90 day study: 2-2.5 months; 333 day study: 6 weeks
- Housing: separated by sex
- Diet: ad libitum
- Water: ad libitum

Administration / exposure

Route of administration:

intramuscular

Vehicle:

water

Details on exposure:

Each of 5 male and 5 female BD (cPah) rats received intramuscular injections of 0, or 200 mg/d methenamine for 90 days.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

90 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, or 200 mg/d methenamine (about 800 mg/kg bw/d in males and 1100 mg/kg bw/d in females, calculated on an assumed mean body weight of 250 g for male rats and 180 g for females)

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Details on study design:

Each of 5 male and 5 female BD (cPah) rats received intramuscular injections of 0, or 200 mg/d methenamine for 90 days (about 800 mg/kg bw/d in males and 1100 mg/kg bw/d in females, calculated on an assumed mean body weight of 250 g for male rats and 180 g for females, purity unspecified).

Examinations

Observations and examinations performed and frequency:

Parameters observed: mortality, clinical signs, behaviour, body weight gain and feed consumption
There were no data on hematology and clinical biochemistry.

Sacrifice and pathology:

Macroscopic and histopathological observations

Other examinations:

none

Statistics:

none

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

No differences from controls in behaviour, body weight gain and feed consumption in rats of both sexes were observed. The only clinical sign observed in animals of both sexes treated with methenamine was a citrus-yellow discoloration of the hair coat. No treatment-related macroscopic or histopathological findings were available.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

800 mg/kg bw/day (nominal)

Sex:

male

Basis for effect level:

other: no adverse effects observed.

2

Dose descriptor:

NOAEL

Effect level:

1 100 mg/kg bw/day (nominal)

Sex:

female

Basis for effect level:

other: no adverse effects observed.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Based on the results of this study, about 800 mg/kg bw/d in males and 1100 mg/kg bw/d in females are considered to be the no observed- adverse-effect-level (NOAELsys) for methenamine by intramuscular injection for 90 days.

Executive summary:

Each of 5 male and 5 female BD (cPah) rats received intramuscular injections of 0, or 200 mg/d methenamine for 90 days (about 800 mg/kg bw/d in males and 1100 mg/kg bw/d in females, calculated on an assumed mean body weight of 250 g for male rats and 180 g for females, purity unspecified). There were no data on hematology and clinical biochemistry. No differences from controls in behaviour, body weight gain and feed consumption in rats of both sexes were observed. The only clinical sign observed in animals of both sexes treated with methenamine was a citrus-yellow discoloration of the hair coat. No treatment-related macroscopic or histopathological findings were available. Based on the results of this study, about 800 mg/kg bw/d in males and 1100 mg/kg bw/d in females are considered to be the no observed- adverse-effect-level (NOAELsys) for methenamine by intramuscular injection for 90 days.