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EC number: 200-471-4 | CAS number: 60-34-4
- 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
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Ancient study prior to GLP, non-guideline and non-specific analytical follow-up. 6-month exposure of rats should not be interpreted after 3rd month because controls were invalidated by heating equipment malfunction leading to control rat weight loss after 13th week. Reported data are reliable but a large amount of required data are missing or not reported.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 971
- Report date:
- 1971
Materials and methods
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- A series of 6-month MMH chronic exposures to four animal species was undertaken to evaluate the safety factor and appropriateness of the current TLV for health of workmen.
- GLP compliance:
- no
- Remarks:
- prior to GLP
- Limit test:
- no
Test material
- Reference substance name:
- Methylhydrazine
- EC Number:
- 200-471-4
- EC Name:
- Methylhydrazine
- Cas Number:
- 60-34-4
- Molecular formula:
- CH6N2
- IUPAC Name:
- methylhydrazine
Constituent 1
Test animals
- Species:
- other: see below
- Strain:
- other: see below
- Details on test animals or test system and environmental conditions:
- Each of the experimental animal groups, as well as their controls, consisted of 8 beagle dogs, 4 rhesus monkeys, 50 Wistar strain rats, and 40 ICR mice. All animals were female except for rats.
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- not specified
- Vehicle:
- not specified
- Remarks on MMAD:
- MMAD / GSD: not applicable (vapour)
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The chamber MMH concentrations were continuously monitored and controlled using a colorimetric method with an AutoAnalyzer. This method is not specific.
- Duration of treatment / exposure:
- 6 months in all animals except half of the dogs
At the end of the first series of experiments, half of the dogs were held for 30 days postexposure observation to determine
reversibility.
+ 4 additional weeks (7 months exposure without reversibility period) in the other half of the dogs
In this summary, the rat data are ignored after week 13 due to invalidation of controls (heating problem - weight loss). - Frequency of treatment:
- Exposures were conducted on a 6-hour/day 5-day/week basis at 0, 0.2, 1, 2 and 5 ppm MMH in four experiments.
Another experiment was conducted by continuous exposure at 0.2 ppm
- No. of animals per sex per dose:
- see above
- Control animals:
- yes
Examinations
- Observations and examinations performed and frequency:
- - weighed biweekly during the studies
- series of 15 clinical chemistry and 8 hematology tests (not conducted on rodents) biweekly during the studies - Sacrifice and pathology:
- All exposed and control animals were sacrificed at the conclusion of the study and submitted for gross necropsy. Major organs from all dogs, monkeys, 10 rats, and 10 mice from each group were saved for histopathologic examination. Bone marrow studies on dogs were also performed at this time for their myeloid and erythroid elements (M/E ratio).
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- Survival (no data on clinical signs):
- 15% and 27% deaths in mice at 2 and 5 ppm
Body weight:
- decreased in rats, except at 0.2 ppm intermittent exposure
Hematology: not investigated in rodents
- increase in methemoglobin, RBC fragility and/or Heinz bodies: at all dose-levels in dogs and monkeys
- decrease in RBC count, hematocrit and/or hemoglobin: at all dose-levels in dogs and monkeys
overall: clear dose-relationship and no apparent threshold for these effects; poorly time-dependent (maximal effect appears already during first month; the effect amplitude tends to decrease along prolonged exposure)
Clinical chemistry:
- mean bilirubin, alkaline phosphatase, and total inorganic phosphorus values for all exposed dog groups were increased: intrahepatic choleostasis
Pathology: done in dogs only:
- decrease in M/E ratio at all doses
Effect levels
open allclose all
- Dose descriptor:
- LOAEC
- Remarks:
- dog and monkey - hemolytic anemia
- Effect level:
- 0.2 ppm
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: intermittent exposure (6h/day 5day/week 6 months)
- Dose descriptor:
- NOEC
- Remarks:
- rats - growth (no data on hemolysis)
- Effect level:
- 0.2 ppm
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: intermittent exposure (6h/day 5d/week, 13 weeks because of invalid controls thereafter) NOAEC may not cover hemolytic anemia (not investigated)
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Executive summary:
Chronic MMH inhalation leads to lethality in mice and decreased body weight gain in rats. In dogs and monkeys, it produces a dose-related hemolytic anemia (not investigated in rodents) with Heinz body formation for which there appears to be no threshold effect level. The anemia is reversible with removal from further exposure at least up to a level of 5 ppm intermittent exposure.
In dogs and monkeys, the 6-month intermittent exposure (6 h/day, 5 days/week) LOAEC was 0.2 ppm (nominal) due to hemolysis. In rats, the 3-month (longer exposure was not validated by appropriate controls) apparent NOEC was 0.2 ppm (nominal) but a large variety of required investigations were not carried out or reported, notably hematological investigations.
The maximal hematological effect appeared already during the first month, plateaued, and gradually the effect amplitude tended to decrease along prolonged exposure.
It may well be asked where man fits in the spectrum of species responses seen with MMH chronic exposure. In a study of the in vitro formation of methemoglobin by MMH (Leahy, 1970), blood samples from four species were compared to determine their equilibrium conversion rates for oxyhemoglobin. In this study, man was found to rank next to the dog in susceptibility with a higher conversion equilibrium than the rat and monkey.
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