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EC number: 200-316-0 | CAS number: 57-14-7
- 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- not indicated in publication
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Some missing data (GLP, methods, test item characterization, clinical signs of toxicity). However the negative result (in bone marrow) is reliable and the positive result (in spermatids) must be taken into account for classification.
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 993
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- (not mentioned in the publication)
- Deviations:
- yes
- Remarks:
- Only one sex tested, without justification
- Principles of method if other than guideline:
- Micronucleus investigated both in somatic cells (erythrocytes as in guideline) and germ cells (spermatids: no applicable guideline)
- GLP compliance:
- not specified
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- N,N-dimethylhydrazine
- EC Number:
- 200-316-0
- EC Name:
- N,N-dimethylhydrazine
- Cas Number:
- 57-14-7
- Molecular formula:
- C2H8N2
- IUPAC Name:
- 1,1-dimethylhydrazine
- Details on test material:
- - Name of test material (as cited in study report): 1,1-dimethylhydrazine
- Substance type: monoconstituent
- Composition, Isomers: not applicable
- Physical state, Analytical purity, Impurities, Purity test date, Lot/batch No, Expiration date, Stability, Storage conditions: not indicated
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River, Saint-Aubin les Elbeuf, France
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 30g
- Fasting period before study: no
- Diet (e.g. ad libitum): UAR A 04, ad lib.
- Water (e.g. ad libitum): tap water, ad lib.
- Assignment to groups, Housing, Acclimation period: not indicated
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Photoperiod (hrs dark / hrs light): 12/12
- Humidity, Air changes: not indicated
IN-LIFE DATES: not indicated
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- - Vehicle(s)/solvent(s) used: water for injection
- Justification for choice of solvent/vehicle: soluble in vehicle
- Concentration of test material in vehicle: not indicated - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
dissolved (soluble at >10% in water) - Duration of treatment / exposure:
- Bone marrow micronucleus test: 2 days
Spermatid micronucleus test: 15 days - Frequency of treatment:
- Bone marrow micronucleus test: 2 injections at 24-h interval
Spermatid micronucleus test: 6 injections (days 0+1 during DNA synthesis phase of preleptotene spermatocytes I; days 7+8 during residual DNA synthesis of pachytene spermatocytes I = crossing-over and chromosome pairing; days 13+14 during meiotic phase of spermatocytes I/II ) - Post exposure period:
- Time of sacrifice, after last injection:
Bone marrow micronucleus test: 24h
Spermatid micronucleus test: 2 days
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
28 mg/kg/injection
Basis:
other: nominal injected dose
- Remarks:
- Doses / Concentrations:
56 mg/kg/injection
Basis:
other: nominal injected dose
- Remarks:
- Doses / Concentrations:
83 mg/kg/injection
Basis:
other: nominal injected dose
- No. of animals per sex per dose:
- 5, males only
- Control animals:
- yes, concurrent vehicle
- other: additional groups indicated as dosed at 0 mg/kg: will be considered as negative controls for this RSS
- Positive control(s):
- In the bone marrow micronucleus test only:
- mitomycin C
- Justification for choice of positive control(s): clastogen
- Route of administration: intraperitoneal
- Doses / concentrations: 1 mg/kg
Examinations
- Tissues and cell types examined:
- - Bone marrow: polychromatic erythrocytes (PCE)
- Testes: Golgi-phase spermatids - Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
Doses were 25, 50 and 75% of the 14-day LD50 (one treatment)
DETAILS OF SLIDE PREPARATION / METHOD OF ANALYSIS / EVALUATION OF TOXICITY:
Bone marrow:
- smears fixed with methanol, stained with MGG
- 2 slides per mouse, at least 1000 PCEs examined for micronucleus per slide.
- Myelotoxicity assessed as the ratio of normochromatic erythrocytes (NE) and PCE , over 200 NE/mouse.
Spermatids:
- On day 16, spermatids isolated by enzymatic dissociation of the testes (trypsin/deoxyribonuclease I). Smears fixed with methanol, stained with 20% Giemsa in Sörensen buffer (pH 7.4)
- 2 slides per mouse, at least 1000 Golgi-phase spermatids examined for micronucleus per slide.
- Testes weight as an indicator of testicular toxicity.
Results and discussion
Test resultsopen allclose all
- Sex:
- male
- Genotoxicity:
- negative
- Remarks:
- Bone marrow PCEs
- Toxicity:
- no effects
- Remarks:
- except for positive control (myelotoxic)
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Sex:
- male
- Genotoxicity:
- positive
- Remarks:
- Golgi-phase spermatids
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- not applicable
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY:
- Clinical signs of toxicity in test animals: the dose-levels were based on the LD50
- Other: no other details indicated
RESULTS OF DEFINITIVE STUDY - Bone marrow assay
- Induction of micronuclei: no statistically significant increase
- Ratio of PCE/NCE: no statistically significant increase
- Appropriateness of dose-levels: justified by absence of excessive cytotoxicity and closeness to LD50
RESULTS OF DEFINITIVE STUDY - Spermatid assay
- Induction of micronuclei: dose-related and biologically significant (up to 5-fold) increase: 0.4, 0.9, 1.2 and 1.9 micronuclei per 1000 spermatids at 0, 28, 56 and 83 mg/kg; p<0.01 at the top-dose.
- Cytotoxicity: no statistically significant effect on testicular weight
- Appropriateness of dose-levels: justified by absence of excessive cytotoxicity and closeness to LD50
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): positive for spermatid assay
The test item was negative in the bone marrow micronucleus assay (2 treatments) but clearly positive in the spermatid micronucleus assay (6 treatments) carried out at the same daily dose-levels. The difference could be related to the number of administrations, leading to an excessive sensitivity of the spermatid assay, for which no guideline exists. However, this spermatid assay shows that the substance is able to induce genetic damage that can not be attributed to overt cytotoxicity (as far as can be judged from the endpoint used, testicular weight).
NB: The authors also obtained positive micronucleus results in the liver, in previous experiments with the test item. - Executive summary:
In order to analyze in vivo micronucleus induction in cells with metabolic enzyme activity, the author compared the sensitivity of somatic and germ cells to four carcinogens in the bone marrow and spermatid micronucleus test in the mouse. Three procarcinogens with a complex metabolic pattern (dimethylnitrosamine, diethylnitrosamine and 1,1-dimethylhydrazine) and one direct unstable mutagen (beta-propiolactone) were tested. All four carcinogens were not detected by the bone marrow micronucleus test but were detected in the mouse spermatid micronucleus test in which they induced clear clastogenic effects, as was the case in a previous study in liver micronucleus test. In conclusion, this study demonstrates that the bone marrow micronucleus test is not sufficient for the prediction of a clastogenic hazard in germ cells. In addition to a second in vivo test in an organ with metabolic enzymes, i.e., the liver, the spermatid micronucleus test can be performed when a specific risk to the testis is likely.
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