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EC number: 225-533-8 | CAS number: 4904-61-4
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Ames
1996: Comparable to OECD 471; GLP; 10, 50, 100, 500, 1000, 2500, and 5000 µg/plate; TA 1535, TA 97a, TA 98, TA 100, and E. coli WP2 uvrA; no evidence for mutagenicity (K2)
Chromosome aberration
1997: Comparable to OECD 471; GLP; 0.25-5.0 mg/ml; human lymphocytes; no evidence for clastogenicity (K1)
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Principles of method if other than guideline:
- Method: see reference
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- other: Salmonella typhimurium TA97a, TA98, TA100, TA1535; E. coli strain WP2 uvrA (pKM101)
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor induced rat liver S9
- Test concentrations with justification for top dose:
- 0; 10; 50; 100; 500; 1000; 2500; 5000 ug/plate
- Vehicle / solvent:
- dimethyl sulfoxide (DMSO)
- Untreated negative controls:
- yes
- Remarks:
- solvent (vehicle) DMSO
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO (see "Negative control")
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- 2-aminoanthracene, 2-nitrofluorene, sodium azide, ICR 191 acridine, methyl methanesulfonate; solvent DMSO except last three positive controls: deionized water
- Positive control substance:
- other: 2-aminoanthracene, 2-nitrofluorene, sodium azide, ICR 191 acridine, methyl methanesulfonate; solvent DMSO except last three positive controls: deionized water
- Details on test system and experimental conditions:
- Ames test
SYSTEM OF TESTING
- Metabolic activation system: arochlor induced rat liver S9 mix ADMINISTRATION:
- Number of replicates: 3
- Application: solvent dimethyl sulfoxide
- Positive and negative control groups and treatment: positive: 2-aminoanthracene, 2-nitrofluorene, sodium azide, ICR 191 acridine, methyl methanesulfonate; solvent DMSO except last three positive controls: deionized water; negative: DMSO (solvent)
-further details: see reference - Evaluation criteria:
- CRITERIA FOR EVALUATING RESULTS: Positive if the average number of revertants in any strain at any test substance concentration studied was at least 2 times greater than the average of the negative control, and there was a positive dose-response relationship in that same strain.
- Statistics:
- no data
- Species / strain:
- other: Salmonella typhimurium TA97a, TA98, TA100, TA1535; E. coli strain WP2 uvrA (pKM101)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other: not reported
- Additional information on results:
- see reference
- Conclusions:
- The test substance proved to be non-mutagenic in this bacterial reverse mutation assay.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosomal Aberration Test)
- Principles of method if other than guideline:
- details: see reference
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Target gene:
- not applicable
- Species / strain / cell type:
- other: Human Lymphocytes
- Metabolic activation:
- with and without
- Metabolic activation system:
- exogenous metabolic S9 activation
- Test concentrations with justification for top dose:
- 0.25 - 5.0 mg/ml
- Vehicle / solvent:
- acetone
- Untreated negative controls:
- yes
- Remarks:
- acetone
- Negative solvent / vehicle controls:
- yes
- Remarks:
- =see negative control (acetone)
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- positive control without activation: mitomycin C (in water); positive control with activation: cyclophosphamide (in water)
- Positive control substance:
- other: positive control without activation: mitomycin C (in water); positive control with activation: cyclophosphamide (in water)
- Details on test system and experimental conditions:
- SYSTEM OF TESTING:
- Metabolic activation system: arochlor-induced rat liver S9 fraction
- No. of metaphases analyzed: 50 per dose and replicate where possible
ADMINISTRATION:
- Dosing:
Trial 1: 0; 0.25; 0.5; 0.75; 1.0; 2.5 mg/ml
Trial 2: 0; 0.5; 0.75; 1.0, 2.5; 3.5; 5.0 mg/ml
Supplemental harvest 24 hours later from trial 2: 1.0; 2.5; 3.5 mg/ml
- Number of replicates: 2
- Positive and negative control groups and treatment: positive, without activation: mitomycin C (in water) positive, with activation: cyclophosphamide (in water)
- negative control: solvent (acetone)
-further details: see reference - Evaluation criteria:
- CRITERIA FOR EVALUATING RESULTS: The test substance was classified as clastogenic (positive) if the test substance produced a statistically significant increase in percent abnormal cells as compared to the negative control at one or more test concentrations and there was a statistically significant dose-related increase in percent of abnormal cells.
- Species / strain:
- other: human lymphocytes
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other: Moderate cytotoxicity observed as measured by the decrease of MI in concentrations of >= 2.5 mg/ml
- Remarks on result:
- other: other: Human Lymphocytes
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Under the conditions of the study the substance 1,5,9-cyclododecatriene was not clastogenic.
Referenceopen allclose all
MITOTIC INDEX: - Trial 1, 2.5 mg/l: reduced to 43% (non-activated) and 41% (activated) of the negative control - Trial 2, 5.0 mg/l: reduced to 30% (non-activated) and 48% (activated) of the negative control
CYTOTOXIC CONCENTRATION: - With metabolic activation: At 1 mg/l, average generation time (AGT)
was increased 18-19 hours with activation.
Significant increases in AGT were not observed in the non-activated system. - Without metabolic activation: At 1 mg/l, the mitotic index was reduced to 38% of the negative control without
metabolic activation, and 52% of the negative control with activation
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
1996: Comparable to OECD 474; GLP; 500 ppm; at least 5 male Sprague Dawley; no induction of chromosomal aberration; Non-clastogenic, non-aneugenic (K1)
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Principles of method if other than guideline:
- Method: see references
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
- Species:
- rat
- Strain:
- other: Crl:CD (SD) BR
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- - Age: 51 days
- Weight at study initiation: mean 231.4 g
- Route of administration:
- inhalation
- Vehicle:
- air
- Details on exposure:
- ADMINISTRATION: nose-only
- vapour atmosphere generated by metering the liquid test substance into a nebulizer
Sampling times and number of samples:
- Test atmosphere: one sample during each exposure to determine concentration and particle size distribution; result: 3200 +/- 280 mg/m3; mass median aerodynamic diameter 3.6 µm
-atmospheric concentration measured by gas chromatography and gravimetric analysis
-further details: see references
- Duration of treatment / exposure:
- 6 hours each on 2 consecutive days
- Frequency of treatment:
- once per day on 2 consecutive days
- Dose / conc.:
- 500 ppm (nominal)
- Remarks:
- 3300 mg/m3 (aerosol/vapor); 3200 +/- 280 mg/m3 (analytical concentration)
- No. of animals per sex per dose:
- No. of animals per dose: 10 exposed, 5 negative control
- Control animals:
- yes
- Positive control(s):
- Control groups and treatment:
- positive: 40 mg cyclophosphamide/kg by oral intubation
-negative: concurrent houseline air - Tissues and cell types examined:
- Bone marrow: At least 3 slides per rat (fixed, and stained with acridine orange), 2000 PCEs per rat scored for micronuclei, 1000 erythrocytes scored for PCE/NCE ratio ; Representative slides from each rat were examined blindly.
further EXAMINATIONS:
- Clinical observations: during exposure (including alerting stimulus)
- Organs examined at necropsy: marrow from 1 femur
- Body weights: yes - Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Remarks:
- no mortalities
- Additional information on results:
- MORTALITY: no test substance-induced mortality
CLINICAL SIGNS:
- During exposure: no clinical signs, response to alerting stimulus diminished or absent
- After exposure: lethargy and/or irregular respiration.
BODY WEIGHT CHANGES: losses in treated and positive control rats
EFFECT ON MITOTIC INDEX OR PCE/NCE RATIO: No statistically significant depressions in the proportion of PCEs among 1000 erythrocytes were observed.
GENOTOXIC EFFECTS: There were no statistically significant increases in the MNPCE frequency in rats exposed to the test substance. A statistically significant increase in the MNPCE frequency was found in the positive control rats. - Conclusions:
- Under the conditions tested, the test substance did not induce chromosomal aberration in experimental animals and thus, was suggested to be non-clastogenic and non-aneugenic.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
IN VITRO
Bacterial reverse mutation assay
Two Ames test investigating the genotoxic potential of the test substance are available.
An Ames test using the method by Ames BN et al. (1975) was performed using strains of Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100, and TA 1538. Strains were treated both with and without metabolic activation (Aroclor induced rat S9 liver homogenate) to 10 – 5000 µg/plate of the test substance. The vehicle was DMSO. Appropriate negative and positive controls were included. Mutagenic effects were evaluated if ratio of revertant rates treated/control was >= 2 at <= 5000 µg/plate with generally positive dose-response relationship in any strain. No evidence for a mutagenic potential was found in either strain of S. typhimurium neither with nor without metabolic activation. Cytotoxicity was not reported. Thus, the test substance was suggested to be non-mutagenic under the conditions chosen (1988, K2).
An Ames test was performed comparable to OECD 471 and in compliance with GLP using strains of Salmonella typhimurium TA 1535, TA 97a, TA 98, TA 100, and E. coli WP2 uvrA (pKM101). Strains were treated both with and without metabolic activation (Aroclor induced rat S9 liver) to 10, 50, 100, 500, 1000, 2500, and 5000 µg/plate of the test substance. The vehicle was DMSO. Appropriate negative and positive controls were included. Mutagenic effects were evaluated if ratio of revertant rates treated/control was >= 2 at <= 5000 µg/plate with generally positive dose-response relationship in any strain. No evidence for a mutagenic potential was found in either strain of S. typhimurium or E. coli neither with nor without metabolic activation. Cytotoxicity was not reported. Thus, the test substance was suggested to be non-mutagenic under the conditions chosen (1996, K2).
In addition, a study which was only available in the original language (Japanese) was available. Strains used were S. typhimurium TA 100, TA 1535, TA 98, and TA 1537 as well as E. coli WP2 uvrA. Strains were treated with concentrations from 0.15 to 5000 µg/plate. In all strains, no evidence of a genotoxic potential was found (2008, K4).
Chromosome aberration
A chromosome aberration test was performed comparable to OECD 473 and in compliance with GLP using human lymphocytes. Cells were treated both with and without metabolic activation to 0.25-5.0 mg/ml of the test substance. The vehicle was acetone. Appropriate negative and positive controls were included. The test substance was classified as clastogenic (positive) if the test substance produced a statistically significant increase in percent abnormal cells as compared to the negative control at one or more test concentrations and there was a statistically significant dose-related increase in percent of abnormal cells. No evidence for a mutagenic potential was found in human lymphocytes neither with nor without metabolic activation. Moderate cytotoxicity observed as measured by the decrease of mitotic index in concentrations of >= 2.5 mg/ml. In trial 1, mitotic index was reduced to 43% (without S9) and 41% (with S9) in comparison to negative control at 2.5 mg/l. In trial 2, mitotic index was reduced to 30% (without S9) and 48% (with S9) in comparison to negative control at 5.0 mg/l. Thus, the test substance was suggested to be non-clastogenic under the conditions chosen (1997, K1).
In addition, a study only available in the original language (Japanese) was available. Chinese hamster lung cells (CHO/IU) were treated with concentrations ranging from 13.3 to 1700 µg/ml. Chromosome aberration was observed in short-term treatment with S9 mix at 27.1, 37.9, and 53.1 µg/ml. However, positive response was associated with high cytotoxicity and thus, was regarded as not substance related (2007, K4).
IN VIVO
Chromosome aberration
To investigate the genotoxic potential of the test substance, an in vivo micronucleus assay comparable to OECD 474 and in compliance with GLP was performed. Five and ten male Sprague Dawley rats in the control and treatment groups, respectively, were exposed via inhalation to 500 ppm of the test substance once per day for six hours on two consecutive days. Cyclophosphamide was included as positive control. At least three slides per rat for bone marrow were fixed and stained with acridine orange and 2000 PCEs per rat were scored for micronuclei and 1000 erythrocytes were scored for PCE/NCE ratio. Representative slides from each rat were examined blindly. Clinical observations were performed during exposure (including altering stimulus) and organs that were examined at necropsy were marrow from one femur. In addition, body weights were also examined. No animal died during the study. No clinical signs were observed during exposure and response to alerting stimulus were diminished or absent. After exposure, lethargy and/or irregular respiration were reported. Decreases in body weight were observed in treated and positive control animals. No statistically significant depressions in the proportion of PCEs among 1000 erythrocytes were observed. There were no statistically significant increases in the MNPCE frequency in rats exposed to the test substance. A statistically significant increase in the MNPCE frequency was found in the positive control rats. Under the conditions tested, the test substance did not induce chromosomal aberrations in experimental animals and thus, was suggested to be non-clastogenic and non-aneugenic (1996, K1).
Justification for classification or non-classification
The available experimental test data are reliable and suitable for the purpose of classification under Regulation 1272/2008. Based on the criteria laid down in Regulation (EC) No. 1272/2008, as amended for the second time in Directive EC 286/2011, classification as a mutagen is not warranted.
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