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EC number: 253-760-2 | CAS number: 38051-10-4
- 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
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Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- February 1994
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 994
- Report date:
- 1994
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- in vitro mammalian chromosome aberration test
Test material
- Reference substance name:
- 2,2-bis(chloromethyl)trimethylene bis(bis(2-chloroethyl)phosphate)
- EC Number:
- 253-760-2
- EC Name:
- 2,2-bis(chloromethyl)trimethylene bis(bis(2-chloroethyl)phosphate)
- Cas Number:
- 38051-10-4
- Molecular formula:
- C13H24Cl6O8P2
- IUPAC Name:
- 2,2-bis(chloromethyl)propane-1,3-diyl tetrakis(2-chloroethyl) bis(phosphate)
- Details on test material:
- Product name: Amgard V6
Appearance: clear to very pale straw coloured viscous liquid
Constituent 1
Method
Species / strain
- Species / strain / cell type:
- lymphocytes: human, primary culture
- Metabolic activation:
- with and without
- Metabolic activation system:
- liver S9, prepared from rats (Sprague-Dawley) treated with Aroclor 1254
- Test concentrations with justification for top dose:
- - without metabolic activation: 39, 78.1, 156.25 micrograms/ml
- with metabolic activation: 78.1, 156.25, 312.5, 625 micrograms/ml - Vehicle / solvent:
- Dimethylsulphoxide (DMSO)
Controls
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- cyclophosphamide for cultures with metabolic activation (25 microgr/mL) Migrated to IUCLID6: cultures without metabolic activation (500 microg/mL)
- Details on test system and experimental conditions:
- Human lymphocytes were evaluated for chromosome aberrations at three dose levels in the absence of S9 and four levels in the presence of S9, together with positive and negative (solvent) controls.
DURATION
- Preincubation period: 48 hours
- Exposure duration: 4 hours (in presence of S9)
- Expression time (cells in growth medium): 16 hours (in presence of S9)
- Exposure duration: 20 h continous in the absence of S9
- Fixation time: cells stored for at least 4 hours (4degree C) to ensure complete fixation
Spindel inhibitor: Demeclocine (0.1 micrg/ml) added two hours before the harvest time
FIXATION: KCl suspension in methanol/glacial acetic acid (3:1 v/v)
STAIN: Gurrs Giemsa R66 (5%)
NUMBER OF CELLS EVALUATED: 100 well-spread metaphases from each culture
DETERMINATION OF CYTOTOXICITY
- Method: 2000 lymphocytes counted and the number of cells in metaphase recorded and expressed as the mitotic index and as percentage of solvent control value
OTHER EXAMINATIONS:
- Determination of polyploidy, endoreduplication - Evaluation criteria:
- A positive response was recorded if the % cells with aberrations markedly exceeded that in the concurrent controls either with or without a clear dose-response relationship. For modest increases in aberration frequency a dose-response relationship is generally required and appropriate statistical tests may be applied in order to record a positive response. Historical control ranges for human primary lymphocytes: 0 to 4% with strucutral aberrations includign gaps and 0 to 2% with structural aberrations excluding gaps and 0 to 1% polyploidy.
- Statistics:
- Frequency of cells with abberations (incl. and excl. gaps) and frequency of polyploid cells are compared to vehicle control using Fisher's Exact test
Results and discussion
Test results
- Species / strain:
- lymphocytes: human lymphocytes from donors
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- - The test substance induced a dose-related decrease in the mitotic index both with and without S9 (maximum dose level with scorable metaphase chromosomes: 156.25 microgr/mL without S9 and 625 microgr/mL with S9).
- In the absence of metabolic activation the total number of gaps was slightly increased (in a dose dependent manner), but the increase did not reach statistical significance.
- Test substance induced a statistically significant inrease in the frequency of cells with chromosome aberrations in one of two replictes at a concentration of 312.5 microgr/mL with metabolic activation only when including gaps. The increase was however not significant when gap type aberrations were excluded, but exceeded the historical maximum of the laboratory. No increase was observed at all other concentrations up to 625 microg/ml also when including gaps. As the effect was not reproducible and not dose related it was concluded to be of no toxicological significance.
Three cells contained chromatic exchange. Additionally a further set of slides prepared from the original cell cultures and evaluated for aberrations did not show these type of aberrations. As this effects was non-reproducible and not dose related, so considered to be of no toxicological significance.
- The test substance did not induce a significant increase in polyploid cells at any dose level in any of the treatments.
Applicant's summary and conclusion
- Conclusions:
- No toxicologically significant increases in the frequency of cells with chromosome aberrations including gaps, either in the presence or absence of a liver enzyme metabolising system (S9) was observed. The test susbstance is therefore considered to be non-clastogenic to human lymphocytes in vitro.
- Executive summary:
In a mammalian cell cytogenetics assay, human lymphocytes were evaluated for chromosome aberrations after exposure to 2,2-bis(chloromethyl)trimethylene bis(bis(2-chloroethyl)phosphate at concentrations of 0 (solvent control), 39, 78.1 and 156.25 microgr/mL without metabolic activation and at 0, 78.1, 156.25, 312.5 and 625 microgr/mL with metabolic activation.
Ethyl methanesulphonate (EMS) and cyclophosphamide were used as positive controls, both induced the appropriate response. There was no dose-related positive response of chromosome aberrations after exposure to the test substance compared to the solvent control. At the mid dose (312.5 microgr/mL) with metabolic activation an significant increase in the frequency of cells with chromosome aberrations was observed when including gaps, but not when excluding gaps (but still higher than the historical maximum of the institute). This was not reproducible in a second set of slides at the same concentration and no dose response was observed. Therefore the effect was not considered toxicologically relevant and it can be concluded from this study that the test substance was not clastogenic in this study.
This GLP study is conducted according to OECD Guideline No.473 and is classified as acceptable.
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