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EC number: 241-158-2 | CAS number: 17091-31-5
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
The test item Bromo(hexahydro-2H-azepin-2-onato-N)magnesium is considered as "not mutagenic under the conditions of the test".
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 01/2008 to 05/2008
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 07072601
- Expiration date of the lot/batch: 26.07.2008
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature 20 ± 5 °C
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: no - Species / strain / cell type:
- other: TA 97a, TA 98, TA 100, TA 102 and TA 1535
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- 4986 to 50 μg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: water
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- benzo(a)pyrene
- other: 4-Nitro-1,2-phenylene diamine (NPD) in DMSO, 2-Amino anthracene (2-AA) in DMSO
- Details on test system and experimental conditions:
- Plate incorporation method
Per strain and dose, four plates with and four plates without S9 mix were used. 10 ml of
the test solution of the appropriate concentration were membrane filtrated into sterile vessels.
Top agar basis was melted in a microwave oven, after melting, 10 ml of histidinebiotin-
solution 0.5 mMol per 100 ml basis was added and the bottle was placed in the
water bath at 45 °C.
0.1 ml of the appropriate solution of the test item were given into a sterile tube. After mixing
with 0.1 ml overnight culture of the respective strain and 0.5 ml phosphate buffer
(only for treatments without S9) or 0.5 ml S9 mix, 2 ml Top-Agar were added. The mixture
was gently vortexed, then poured on a minimal glucose plate and distributed evenly,
using a Drigalski spatula. The plates were closed, covered with brown paper and left to
harden for a few minutes, then inverted and placed in the dark incubator at 37 °C.
Pre-incubation method
Per strain and dose, four plates with and four plates without S9 mix were used. 10 ml of
the test solution of the appropriate concentration were membrane filtrated into sterile vessels.
Top agar basis was melted in a microwave oven, after melting, 10 ml of histidinebiotin-
solution 0.5 mMol per 100 ml basis was added and the bottle was placed in the
water bath at 45 °C.
0.1 ml of the appropriate solution of the test item were given into a sterile tube. After mixing
with 0.1 ml overnight culture of the respective strain, 0.5 ml phosphate buffer (only
for treatments without S9) or 0.5 ml S9 mix were added. The mixture was incubated in an
incubation chamber at 37°C for 20 minutes. During this time the vessels were aerated
through careful shaking. Then 2 ml top agar were added. The mixture was vortexed gently,
then poured on a minimal glucose plate and distributed evenly, using a Drigalski spatula.
The plates were closed, covered with brown paper and left to harden for a few minutes,
then inverted and placed in the dark incubator at 37 °C. - Evaluation criteria:
- The colonies were counted visually, the numbers were recorded.
- Statistics:
- A spreadsheet software (Microsoft Excel®) was used to calculate mean values and standard deviations as well as the increase factor of revertant induction.
- Species / strain:
- S. typhimurium TA 97
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Conclusions:
- Under the conditions of the test, the test item didn't show mutagenic effects towards Salmonella typhimurium, strains TA 97a, TA 98, TA 100, TA 102 and TA 1535. Therefore, no concentration-effect relationship could be determined.
- Executive summary:
The test item Bromo(hexahydro-2H-azepin-2-onato-N)magnesium is considered as "not mutagenic under the conditions of the test".
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
The test item Bromo(hexahydro-2H-azepin-2-onato-N)magnesium did not induce micronuclei as determined by the micronucleus test in the bone marrow cells of the mouse.
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 09/2008 to 11/2008
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mouse spot test
- Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 07072601
- Expiration date of the lot/batch: July 2009
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Housing: single
Cage Type: Makrolon Type I, with wire mesh top (EHRET GmbH, D-79302 Emmendingen)
Bedding: granulated soft wood bedding (Harlan Laboratories GmbH, D-33178 Borchen)
Feed: pelleted standard diet, ad libitum (Harlan Laboratories GmbH, D-33178 Borchen)
Water: tap water, ad libitum, (Gemeindewerke, D-64380 Roßdorf)
Environment: temperature 22 ± 3 °C
relative humidity 30 - 70 %
artificial light 6.00 a.m. - 6.00 p.m. - Route of administration:
- oral: gavage
- Vehicle:
- deionised water
- Duration of treatment / exposure:
- single administration of the test item
- Frequency of treatment:
- once
- Post exposure period:
- 24 h and 48 h, respectively
- Dose / conc.:
- 437.5 mg/kg bw/day (nominal)
- Dose / conc.:
- 875 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 750 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 6
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Yes, cyclophosphamide
- Tissues and cell types examined:
- bone marrow cells
- Details of tissue and slide preparation:
- The animals were sacrificed using CO2 followed by bleeding. The femora were removed,
the epiphyses were cut off and the marrow was flushed out with foetal calf serum using a
syringe. The cell suspension was centrifuged at 1500 rpm (390 x g) for 10 minutes and
the supernatant was discarded. A small drop of the re-suspended cell pellet was spread
on a slide. The smear was air-dried and then stained with May-Grünwald (Merck, D-64293
Darmstadt)/Giemsa (Merck, D-64293 Darmstadt). Cover slips were mounted with EUKITT
(Kindler, D-79110 Freiburg). At least one slide was made from each bone marrow sample. - Evaluation criteria:
- Evaluation of the slides was performed using NIKON microscopes with 100x oil immersion
objectives. At least 2000 polychromatic erythrocytes (PCE) were analysed per animal for
micronuclei. To describe a cytotoxic effect the ratio between polychromatic and
normochromatic erythrocytes was determined in the same sample and expressed in
polychromatic erythrocytes per 2000 erythrocytes. The analysis was performed with
coded slides. - Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- The test item Bromo(hexahydro-2H-azepin-2-onato-N)magnesium was assessed in the
micronucleus assay for its potential to induce micronuclei in polychromatic erythrocytes
(PCE) in the bone marrow of the mouse.
The test item was formulated in deionised water, which was also used as vehicle control.
The volume administered orally was 10 mL/kg b.w.. 24 h and 48 h after a single
administration of the test item the bone marrow cells were collected for micronuclei
analysis.
Where possible twelve animals (6 males, 6 females) per test group were evaluated for the
occurrence of micronuclei. At least 2000 polychromatic erythrocytes (PCEs) per animal
were scored for micronuclei.
To describe a cytotoxic effect due to the treatment with the test item the ratio between
polychromatic and normochromatic erythrocytes was determined in the same sample and
reported as the number of PCEs per 2000 erythrocytes.
The following dose levels of the test item were investigated:
24 h preparation interval: 437.5, 875 and 1750 mg/kg b.w..
48 h preparation interval: 1750 mg/kg b.w..
As estimated by a pre-experiment 1750 mg Bromo(hexahydro-2H-azepin-2-onato-
N)magnesium per kg b.w. was suitable. In the main study 1 female (animal no. 72) died
after treatment with this dose.
The mean number of polychromatic erythrocytes was not decreased after treatment with
the test item as compared to the mean value of PCEs of the vehicle control indicating that
Bromo(hexahydro-2H-azepin-2-onato-N)magnesium did not have any cytotoxic properties
in the bone marrow.
In comparison to the corresponding vehicle controls there was no biologically relevant
enhancement in the frequency of the detected micronuclei at any preparation interval and
dose level after administration of the test item. A statistically significant enhancement in
the frequency of micronucleated cells was observed in the groups treated with the mid
dose and high dose (prepared at the 48 h preparation interval). This increase was,
however, not dose related in the case of the mid dose. For the high dose there was not
any indication why the effect should turn up at the later interval without any prior signs
(such as organ toxicity) at the 24 h interval. Furthermore, all obtained values were within
the historical vehicle control range. Therefore, the significant increases are regarded as
biologically irrelevant.
40 mg/kg b.w. cyclophosphamide administered orally was used as positive control which
showed a statistically significant increase of induced micronucleus frequency. - Executive summary:
In conclusion, it can be stated that during the study described and under the experimental
conditions reported, the test item did not induce micronuclei as determined by the
micronucleus test in the bone marrow cells of the mouse.
Reference
|
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Justification for classification or non-classification
No classification according to CLP-regulation required due to negative results in in-vitro OECD 471 study and in-vivo OECD 474 study.
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