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EC number: 428-650-4 | CAS number: 153719-23-4
- 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 26 Sep 1995 to 22 Nov 1995
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 995
- Report date:
- 1995
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- 1983
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OTS 798.5395 (In Vivo Mammalian Cytogenics Tests: Erythrocyte Micronucleus Assay)
- Version / remarks:
- 1987
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- 1992
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
- Version / remarks:
- 1987
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- mammalian erythrocyte micronucleus test
Test material
- Reference substance name:
- 3-(2-chloro-thiazol-5-ylmethyl)-5-methyl-[1,3,5]oxadiazinan-4-ylidene-N-nitroamine
- Cas Number:
- 153719-23-4
- Molecular formula:
- C8H10ClN5O3S
- IUPAC Name:
- 3-(2-chloro-thiazol-5-ylmethyl)-5-methyl-[1,3,5]oxadiazinan-4-ylidene-N-nitroamine
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- Tif:MAGf
- Remarks:
- (SPF)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 24 - 38 g
- Housing: Housed individually or 2 per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.5-21.0
- Humidity (%): : 44-76
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES:
26 Sep 1995 to 22 Nov 1995
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle used: Bistilled water
- Amount of vehicle: 10 mL/kg - Frequency of treatment:
- Single dose
- Post exposure period:
- 16, 24 and 48h. An overview of the terminations times for the different treatment and control groups can be found in Table 1 in 'Any other information on materials and methods incl. tables'.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 312.5 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 625 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 250 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- Vehicle control: 15 animals/sex
Positive control: 5 animals/sex
312.5 and 625 mg/kg bw: 5 animals/sex
1000 mg/kg bw: 15 males and 5 females (+3 reserve males)
1250 mg/kg bw: 10 females (+3 reserve females) - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- - Positive control: Cyclophosphamide
- Route of administration: Oral (gavage)
- Doses / concentrations: 64 mg/kg
Examinations
- Tissues and cell types examined:
- Femoral bone marrow / polychromatic erythrocytes
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: A preliminary MTD study was performed in mice by the fixed dose procedure at dose levels up to 2000 mg/kg, to determine the highest dose level producing significant toxicity but not death. A solubility test was conducted to determine the highest applicable dose level.
DETAILS OF SLIDE PREPARATION: Bone marrows were harvested from the femurs with foetal calf serum. The bone marrow suspension was centrifuged and the cells re-suspended in foetal calf serum and smears made. The slides were air-dried and stained with May-Grűnwald/ Giemsa solution.
METHOD OF ANALYSIS: Slides were coded and scored blind. Slides of 5 animals/ sex/ dose, showing good differentiation between mature and polychromatic erythrocytes were scored. For each animal the ratio of polychromatic to normochromatic erythrocytes was determined and 2000 polychromatic erythrocytes were scored for micronuclei. - Evaluation criteria:
- - Negative effect – if there was no statistically significant difference (Chi-Square ≤ 3.84; p ≥ 0.05) between the mean number of micronucleated PCEs in the groups treated with the test substance and that of the respective negative control and the former did not exceed the range accepted for the negative control (≤ 0.20%).
- Positive Effect - if, in any group with the test substance, the mean number of micronucleated PCEs exceeds the value of 0.20% and if there was a statistically significant difference (Chi-Square > 3.84; p < 0.05) of the number of micronucleated PCEs in comparison with the negative control. - Statistics:
- The significance of differences was assessed by the Chi-Square-Test (p<0.5).
Results and discussion
Test results
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: 0 - 2000 mg/kg bw
- Solubility: Bidistilled water was found to be the most appropriate vehicle giving a suspension at the highest dose of 3750 mg/kg.
- Clinical signs of toxicity in test animals: Both animals treated with 2000 mg/kg died within 1-3 hours of treatment. Animals dosed with 1250 mg/kg showed clinical signs. Clinical signs were also recorded at the lower doses. In the confirmatory experiment both animals survived but showed clinical signs. 1250 mg/ was selected as the high dose for the micronucleus test.
RESULTS OF DEFINITIVE STUDY
- Toxicity: The dose level of 1250mg/kg bw caused death in 7/13 females and this dose was reduced to 1000 mg/kg. Treatment at 1000mg/kg bw produced signs of toxicity including lethargy, hunched posture and ataxia. Some animals treated at 625mg/kg bw also showed reduced locomotor activity.
- Ratio of PCE/NCE: The ratios of polychromatic to normochromatic erythrocytes after treatment with the test substance indicated no effects on erythropoiesis at any dose level (Table 1 in 'Any other information on results, incl. tables').
Any other information on results incl. tables
Table 1. Percentage of MNPCE (PCE/NCE ratio) at different preparation times
Treatment |
Dose |
|
% MNPCE (PCE/NCE ratio) |
||
|
16 hours |
24 hours |
48 hours |
||
Vehicle Control |
10 mL/kg |
males females combined |
0.03 (0.68) 0.03 (1.27) 0.03 (0.98) |
0.07 (0.63) 0.02 (1.20) 0.05 (0.92) |
0.04 (0.63) 0.08 (1.02) 0.06 (0.83) |
test substance1 |
1000 mg/kg |
males females combined |
0.04 (0.74) 0.06 (0.91) 0.05 (0.83) |
0.09 (0.87) |
0.05 (0.75) |
test substance 2 |
1250 mg/kg |
female |
- |
0.04 (0.81) |
0.02 (1.16) |
test substance |
625 mg/kg |
males females combined |
- |
0.01 (0.68) 0.01 (0.88) 0.01 (0.78) |
- |
test substance |
312.5 mg/kg |
males females combined |
- |
0.02 (0.84) 0.00 (0.86) 0.01 (0.85) |
- |
Positive control |
64 mg/kg |
males females combined |
|
3.28* (0.91) 1.10* (0.95) 2.19* (0.93) |
|
* p < 0.05 (Chi-Square Test) 10000 PCEs counted per group 1Due to symptoms of toxicity the dose level was reduced to 1000 mg/kg. 2Females for 24 and 48 hours sampling were treated with 1250 mg/kg, which proved highly toxic. |
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of the test, performed accoring to OECD 474 under GLP, the test substance was not clastogenic or aneugenic in the in vivo mouse bone marrow micronucleus test.
- Executive summary:
In an in vivo bone marrow micronucleus assay, performed accoring to OECD 474 under GLP, five male and five female Tif:MAGf young adult mice per group were given a single oral dose of 1000 (or 1250 females 24 and 48 hours), 625.0 or 312.5 mg/kg bw test substance. In addition, five male and five female mice were dosed with10 mL/kg bw bidistilled water (vehicle control) and five male and five female mice with 64 mg/kg bw cyclophosphamide (positive control). From the high dose and negative control groups the animals were killed 16, 24 or 48 hours after dosing. From the intermediate and low dose and positive control group animals were sacrificed 24 hours after application. Subsequently femoral bone marrow cells were prepared and polychromatic erythrocytes were scored for micronuclei.
The highest dose of 1250 mg/kg applied to females (24 and 48 hours) caused significant toxicity, manifested as premature death of several animals 4 to 5 hours after treatment. The high dose of 1000 mg/kg applied to males (all sampling times) and to females (16 hour sampling time) caused clinical signs in several animals. In all dosage groups assessed at the different periods post treatment, no statistically significant increase in the incidence of micronucleated polychromatic erythrocytes was observed when compared to the respective negative control group. The test system positive control, induced statistically and biologically significant increases in the frequency of micronucleated polychromatic erythrocytes at the 24 hour sampling time.
In conclusion, under the conditions of the test, the test substance was neither clastogenic nor aneugenic in the in vivo mouse bone marrow micronucleus test.
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