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EC number: 202-905-8 | CAS number: 100-97-0
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Toxicity to reproduction
Administrative data
- Endpoint:
- three-generation reproductive toxicity
- Remarks:
- based on test type
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1970
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: old public available literature (no GLP, non guideline)
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- publication
- Title:
- Studio della tossicita transplacentare edi cancerogenesi in ratti trattati con esametilentetramina
- Author:
- Della Porta, G.; Cabral, J. R.; Parminani, G.
- Year:
- 1 970
- Bibliographic source:
- Tumori, 56: 325-334, 1970
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:
- no
Test material
- 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:
- not indicated.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - 3-4 rats per cage
- diet and water ad libitum
Administration / exposure
- Route of administration:
- oral: drinking water
- Vehicle:
- water
- Details on exposure:
- Rats were given 1% methenamine in drinking water for three successive generations, up to the age of 40 weeks in the F1 and F2 groups and of 20 weeks for the F3 group, thereafter all groups were kept under observation up to week 130 of their lifetime.
An additional test group of 5 females was run on 2% methenamine from mating through lactation. - Details on mating procedure:
- F0: 1 male was mated with 2 females (no further details given).
F1: 3 males were mated with 7 females
F2: 4 males were mated with 11 females - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- no details on analytical verification of doses.
- Duration of treatment / exposure:
- F0: 4 weeks before mating, 25-30 days of pregnancy (no further details given on F0 generation)
F1: total treatment 40 weeks, mating in week 26
F2: total treatment 40 weeks, mating in week 15
F3: total treatment 20 weeks - Frequency of treatment:
- continuous via the drinking water.
- Details on study schedule:
- Rats were given 1% methenamine in drinking water for three successive generations, up to the age of 40 weeks in the F1 and F2 groups and of 20 weeks for the F3 group, thereafter all groups were kept under observation up to week 130 of their lifetime. The parental generation (F0) group consisted of one male and two females that were given 1% methenamine in drinking water during four weeks before mating. The treatment of the females continued until two litters of ten pups each had been weaned. The descendant F1 groups consisted of 13 males and 7 females. The females were mated to 3 males of their group. One dam died during delivery while the remaining 6 dams gave birth to a total of 36 pups from which 10 died during lactation. The resulting F2 group consisted of 15 males and of 11 females. These females were mated to 4 males of their group and delivered a total of 99 pups from which only 12 males and 12 females were further raised to yield the F3 group.
An additional test group of 5 females was run on 2% methenamine from mating through lactation. They delivered a total of 49 pups from which 16 animals per sex were continued on 2% methenamine for 50 weeks. All groups were kept under observation for over two years of age.
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0, 1 % (daily intake of approximately 1.5-2 g/kg bw/d for males and of 2-2.5 g/kg bw/d for females)
Basis:
nominal in water
3 generation study
- Remarks:
- Doses / Concentrations:
0, 2 % (daily intake of approximately 3.0-4.0 g/kg bw/d for males and of 4.0-5.0 g/kg bw/d for females)
Basis:
nominal in water
additional one generation study
- No. of animals per sex per dose:
- F0: 2 females and 1 males
F1: 7 females, 13 males
F2: 11 females, 15 males
F3: 99 pups in total, 12 of each sex were selected for treatment for an other 20 weeks - Control animals:
- yes, plain diet
- Details on study design:
- no further details given.
- Positive control:
- no positive control.
Examinations
- Parental animals: Observations and examinations:
- - water intake
no further details on F0 animals observations given.
F1, F2 and F3 animals: mortality, body weights, clinical symptoms - Oestrous cyclicity (parental animals):
- not examined.
- Sperm parameters (parental animals):
- not examined.
- Litter observations:
- - number and sex of litters
- body weigh and body weight gain - Postmortem examinations (parental animals):
- not details given.
- Postmortem examinations (offspring):
- - pathology (macroscopic and microscopic) of organs (carcinogenicity)
- Statistics:
- Student's t-test
- Reproductive indices:
- not calculated/examined.
- Offspring viability indices:
- not calculated/examined.
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Organ weight findings including organ / body weight ratios:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Other effects:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
Details on results (P0)
Effect levels (P0)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 500 - <= 2 500 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects on parental animals were reported.
Target system / organ toxicity (P0)
- Key result
- Critical effects observed:
- no
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- mortality observed, treatment-related
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
Details on results (F1)
Anymore detailed information on reproductive endpoints is not available from this study since it had been primarily directed to elucidate carcinogenicity.
Results: F2 generation
Effect levels (F2)
- Key result
- Dose descriptor:
- LOAEL
- Generation:
- F2
- Effect level:
- >= 1 500 - <= 2 500 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: Postnatal mortality was observed in the weanlings (F2 generation) of the methenamine exposed groups.
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Postnatal mortality was observed in the weanlings (F2 generation) of the methenamine exposed groups. Reproductive capacity and capability was not affected during this study. Thus, the dosage of 1.5-2.5 g /kg bw/day may represent a LOAEL for developmental toxicity. The doses used exceed the recommended maximum doses in respective OECD/EU guidelines.
- Executive summary:
In a further study on transplacental toxicity and carcinogenesis with Wistar rats, the outcome of the exposure of animals to methenamine via drinking water was followed up in two independent experiments for one and for three successive generations. The results of the first experiment are presented in a separate endpoint study record.
In a second experiment rats were given 1% methenamine in drinking water for three successive generations, up to the age of 40 weeks in the F1 and F2 groups and of 20 weeks for the F3 group, thereafter all groups were kept under observation up to week 130 of their lifetime. The parental generation (F0) group consisted of one male and two females that were given 1% methenamine in drinking water during four weeks before mating. The treatment of the females continued until two litters of ten pups each had been weaned. The descendant F1 groups consisted of 13 males and 7 females. The females were mated to 3 males of their group. One dam died during delivery while the remaining 6 dams gave birth to a total of 36 pups from which 10 died during lactation. The resulting F2 group consisted of 15 males and of 11 females. These females were mated to 4 males of their group and delivered a total of 99 pups from which only 12 males and 12 females were further raised to yield the F3 group. An additional test group of 5 females was run on 2% methenamine from mating through lactation. They delivered a total of 49 pups from which 16 animals per sex were continued on 2% methenamine for 50 weeks. All groups were kept under observation for over two years of age. The survival rates of all raised offspring generations (except F2 generation) were not affected by any treatment and the body weights did not show significant differences between control and treated groups. Anymore detailed information on reproductive endpoints is not available from this study since it had been primarily directed to elucidate carcinogenicity. The doses used exceed the recommended maximum doses in respective OECD/EU guidelines.
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