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EC number: - | CAS number: -
- 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 vitro
Administrative data
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 27 June 2007 to 08 August 2007
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 007
- Report date:
- 2007
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
- GLP compliance:
- yes
- Type of assay:
- other: in vitro mammalian chrosome aberration test
Test material
Reference
- Name:
- Unnamed
- Type:
- Constituent
- Type:
- impurity
- Test material form:
- solid: particulate/powder
- Details on test material:
- The test material is a UVCB substance.
- Specific details on test material used for the study:
- Identification AD-2000
Form White powder
Batch L-620150
Storage At room temp in the dark
Stability under storage condition Stable
Expiry date 1 January 2009
Method
Species / strain
- Species / strain / cell type:
- mammalian cell line, other:
- Details on mammalian cell type (if applicable):
- Cultured peripheral human lymphocytes were used.
Blood was collected from healthy adult, non-smoker, male volunteers. The Average Generation Time (AGT) of the cells and the age of the donor at the time the AGT was determined (December 2006) and are presented below:
Dose range finding study: age 30, AGT = 13.5 h First cytogenetic assay: age 34, AGT = 14.4 h Second cytogenetic assay: age 36, AGT = 13.9 h
- Metabolic activation:
- with and without
- Metabolic activation system:
- phenobarbital and ß-naphthoflavone induced rat liver S9-mix
- Test concentrations with justification for top dose:
- With S9 mix: 3, 10 and 33 µg/ml culture medium
(3 h exposure time, 48 h fixation time).
Without S9 mix: 3, 10 and 100 µg/ml culture medium
(24 h exposure time, 24 h fixation time).
3, 10 and 100 µg/ml culture medium
(48 h exposure time, 48 h fixation time).
Justification
In order to select the appropriate dose levels for the chromosome aberration test cytotoxicity data were obtained in a dose range finding test the test substance was tested in the absence and in the presence of 1.8% (v/v) S9-fraction.
Lymphocytes (0.4 ml blood of a healthy male donor was added to 5 ml or 4.8 ml culture medium, without and with metabolic activation respectively and 0.1 ml (9 mg/ml) Phytohaemagglutinin) were cultured for 48 h and thereafter exposed to selected doses of
the test substance for 3 h, 24 h and 48 h in the absence of S9-mix or for 3 h in the presence of S9-mix.
The highest tested concentration was determined by the solubility of the test substance in the culture medium at the 3 h exposure time. At the 24 and 48 h exposure time, the test substance was tested beyond the limit of solubility to obtain adequate toxicity data.
After 3 h exposure to the test substance in the absence or presence of S9-mix, the cells were separated from the exposure medium by centrifugation (5 min, 150 g). The supernatant was removed and cells were rinsed with 5 ml HBSS. After a second centrifugation step, HBSS was removed and cells were resuspended in 5 ml culture medium and incubated for another 20-22 h (24 h fixation time). The cells that were exposed for 24 hand 48 h in the absence of S9-mix were not rinsed after exposure but were fixed immediately (24 hand 48 h fixation time).
Cytotoxicity of the test substance in the lymphocyte cultures was determined using the mitotic index. - Vehicle / solvent:
- Dimethyl sulfoxide
Controlsopen allclose all
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- mitomycin C
- Remarks:
- Without metabolic activation
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- With metabolic activation
- Details on test system and experimental conditions:
- Cultured peripheral human lymphocytes were used as test system. Blood was collected from healthy adult, non-smoker, male volunteers. The Average Generation Time (AGT) of the cells and the age of the donor at the time the AGT was determined (December 2006) and are presented below:
Dose range finding study: age 30, AGT = 13.5 h First cytogenetic assay: age 34, AGT = 14.4 h Second cytogenetic assay: age 36, AGT = 13.9 h - Evaluation criteria:
- A chromosome aberration test is considered acceptable if it meets the following criteria:
a) The number of chromosome aberrations found in the solvent control cultures should reasonably be within the laboratory historical control data range
b) The positive control substances should produce a statistically significant (Chi-square test, one-sided, p < 0.05) increase in the number of cells with chromosome aberrations.
c) A homogeneous response between the replicate cultures is observed.
d) A possible precipitate present on the slides should not interfere with the scoring of chromosome aberrations. - Statistics:
- A test substance was considered positive (clastogenic) in the chromosome aberration test if:
a) It induced a dose-related statistically significant (Chi-square test, one-sided, p < 0.05)
increase in the number of cells with chromosome aberrations.
b) A statistically significant and biologically relevant increase in the frequencies of the number
of cells with chromosome aberrations was observed in the absence of a clear dose-response relationship
A test substance was considered negative (not clastogenic) in the chromosome aberration test if none of the tested concentrations induced a statistically significant (Chi-square test, one-sided,
p < 0.05) increase in the number of cells with chromosome aberrations.
The preceding criteria are not absolute and other modifying factors might enter into the final evaluation decision.
The incidence of aberrant cells (cells with one or more chromosome aberrations, inclusive or exclusive gaps) for each exposure group outside the laboratory historical control data range was compared to that of the solvent control using Chi-square statistics
x^2=(N-1)(ad-bc)^2/((a+b)(c+d)(a+c)(b+d))
where b = the total number of aberrant cells in the control cultures.
d = the total number of non aberrant cells in the control cultures.
no = the total number of cells scored in the control cultures.
a = the total number of aberrant cells in treated cultures to be compared with the
control.
c = the total number of non aberrant cells in treated cultures to be compared with the
control
n1 = the total number of cells scored in the treated cultures
N = sum of n0 and n1
x^2>(N-1)(ad-bc)^2/((a+b)(c+d)(a+c)(b+d))
is small (p< 0.05) the hypothesis that the incidence of cells with chromosome aberrations is the same for both the treated and the solvent control group is rejected and the number of aberrant cells in the test group is considered to be significantly different from the control group at the
95% confidence level.
Results and discussion
Test results
- Key result
- Species / strain:
- mammalian cell line, other: Cultured peripheral human lymphocytes
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Additional information on results:
- Both in the absence and presence of S9-mix, the test substance did not induce a statistically significant or biologically relevant increase in the number of cells with chromosome aberrations
Both in the absence and presence of S9-mix, the test substance did not increase the number of polyploid cells and cells with endoreduplicated chromosomes
Applicant's summary and conclusion
- Conclusions:
- the test substance is not clastogenic in human lymphocytes under the experimental conditions described in this report.
The ability of the test substance to induce chromosome aberrations in human peripheral lymphocytes was investigated in two independent experiments. The highest concentration analysed was selected based on the solubility of the test substance in the culture medium.
The number of cells with chromosome aberrations found in the solvent control cultures was within the laboratory historical control data range (see Appendix Ill). The number of polyploid cells and cells with endoreduplicated chromosomes in the solvent control cultures was within the laboratory historical control data range (see Appendix IV). The positive control chemicals (MMC-C and CP) both produced statistically significant increases in the frequency of aberrant cells. It was therefore concluded that the test conditions were adequate and that the metabolic activation system (S9-mix) functioned properly.
Both in the absence and presence of S9-mix the test substance did not induce a statistically significant or biologically relevant increase in the number of cells with chromosome aberrations in two independent experiments..
No effects of the test substance on the number of polyploid cells and cells with endoreduplicated chromosomes were observed both in the absence and presence of S9-mix. Therefore it can be concluded that the test substance does not disturb mitotic processes and cell cycle progression and does not induce numerical chromosome aberrations under the experimental conditions described in this report. - Executive summary:
The ability of the test substance to induce chromosome aberrations in human peripheral lymphocytes was investigated in two independent experiments. The highest concentration analysed was selected based on the solubility of the test substance in the culture medium.
The number of cells with chromosome aberrations found in the solvent control cultures was within the laboratory historical control data range (see Appendix Ill). The number of polyploid cells and cells with endoreduplicated chromosomes in the solvent control cultures was within the laboratory historical control data range (see Appendix IV). The positive control chemicals (MMC-C and CP) both produced statistically significant increases in the frequency of aberrant cells. It was therefore concluded that the test conditions were adequate and that the metabolic activation system (S9-mix) functioned properly.
Both in the absence and presence of S9-mix the test substance did not induce a statistically significant or biologically relevant increase in the number of cells with chromosome aberrations in two independent experiments..
No effects of the test substance on the number of polyploid cells and cells with endoreduplicated chromosomes were observed both in the absence and presence of S9-mix. Therefore it can be concluded that the test substance does not disturb mitotic processes and cell cycle progression and does not induce numerical chromosome aberrations under the experimental conditions described in this report.
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