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EC number: 264-598-7 | CAS number: 64001-15-6
- 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 substance is negative in the Ames test based on read across from Cyclacet which is tested in an OECD TG 471.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2-23-2007 - 3-26-07
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Test was conducted according to OECD Test Guideline No. 471, 1997, under GLP Standards and QA.
- Justification for type of information:
- Information used for read across to Cyclacet Dihydro
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 1997
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- His-gene: Amino acid histidine, and Trp-gene: amino acid tryptophan
- Species / strain / cell type:
- other: S. typhimurium TA97a, TA98, TA100, TA 102, TA1535 and E. coli WP2 uvrA (328)
- Details on mammalian cell type (if applicable):
- Not applicable
- Additional strain / cell type characteristics:
- other: S. typhimurium TA97a, TA98, TA100: rfa, ∆uvrB, pKM101 S. typhimurium TA1535: rfa, ∆uvrB S. typhimurium TA102: rfa, pAQ1 Plasmid, pKM101 E. coli WP2 uvrA (328): ∆uvrB
- Metabolic activation:
- with and without
- Metabolic activation system:
- Rat liver S9 induced by Aroclor 1254
- Test concentrations with justification for top dose:
- Plate incorporation assay: 5, 10, 50, 100, 500, 1000, 2500, and 5000 μg/plate
Preincubation assay: 5, 10, 50, 100, and 250 μg/plate - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: Selection of the appropriate solvent and diluent for the test substance was based on solubility information provided by the Sponsor and on a solubility assessment at the testing facility. - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: -S9: S. typhimurium TA97a: ICRI91 Acridine mutagen; S. typhimurium TA98: 2-Nitrofluorene; S. typhimurium TA100 and TA1535: Sodium azide; E. coli WP2 uvrA (328): N-Methyl-N'-nitro-N-nitroguanidine +S9: S. typhimurium TA97a: 9,10-Dimethy1-1,2-benzanthracene
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation); preincubation
DURATION
- Preincubation period: 30 minutes
- Selection time (if incubation with a selection agent): 48-72 hours
SELECTION AGENT (mutation assays): agar containing Histidine or Tryptophan
NUMBER OF REPLICATIONS: 3 plates per concentration
NUMBER OF CELLS EVALUATED: 1 x 10*8 viable cells
DETERMINATION OF CYTOTOXICITY
- Method: determination of a concentration related reduction in the mean number of revertants per plate and/or the reduction of the microcolony background lawns
OTHER EXAMINATIONS:
- Other: The dosage regimen was determined from a solubility study conducted prior to the experimental start. - Evaluation criteria:
- A test substance was classified as positive if either of the first two conditions and the third condition were met:
1) The mean number of revertants in Salmonella strains TA97a, TA98, TA100, TA102 or Escherichia coli WP2 uvrA (328) at any test substance concentration was at least two times greater than the mean in the concurrent vehicle control.
2) The mean number of revertants in Salmonella strains TA1535 or TA1537 at any test substance concentration was at least three times greater than the mean in the concurrent vehicle control.
3) For a positive classification in any strain, there must have been a concentration-related increase in the mean revertants per plate in that same strain.
A test substance was classified as negative (e.g., nonmutagenic in bacteria) if the following conditions were met:
1) There were no test substance concentrations in Salmonella strains TA97a, TA98, TA100, TA102 or Escherichia coli WP2 uvrA (328) with a mean number of revertants that were at least two times greater than the mean in the concurrent vehicle control.
2) There were no test substance concentrations in Salmonella strains TAl535 or TAl537 with a mean number of revertants that were at least three times greater than the mean in the concurrent vehicle control.
3) For a negative classification in any strain, there could not be a concentration related increase in the mean revertants per plate in that same strain. In consultation with the sponsor, negative results may be confirmed as needed.
Results not meeting criteria for positive or negative classification were evaluated using scientific judgment and may have been reported as equivocal. In a two trial study, if one trial is positive and the other is negative, additional trials may be conducted. - Statistics:
- Trials were evaluated independently. For each selected test strain, the average number of revertants and the standard deviation at each concentration level with and without the exogenous metabolic activation system was calculated.
- Key result
- Species / strain:
- other: S. typhimurium TA97a, TA98, TA100, TA 102, TA1535 and E. coli WP2 uvrA (328)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- RANGE-FINDING/SCREENING STUDIES: Due to test substance associated toxicity in the plate incorporation assay, test substance concentrations were lowered for the confirmatory assay.
COMPARISON WITH HISTORICAL CONTROL DATA: The mean number of revertants observed in the negative controls (DMSO) for each of the test strains was within acceptable historical negative control ranges.
ADDITIONAL INFORMATION ON CYTOTOXICITY: Plate incorporation assay: S. typhimurium TA97a, TA98, TA100 and TA1535 (± S9), and E. coli WP2 uvrA (–S9): ≥ 500 ug/plate; E. coli WP2 uvrA (+S9): ≥ 1000 ug/plate.
Preincubation assay (–S9): S. typhimurium TA98: ≥ 100 ug/plate; S. typhimurium TA97a, TA100, TA1535, and E. coli WP2 uvrA (328): 250 ug/plate. - Remarks on result:
- other: all strains/cell types tested
- Conclusions:
- Under the conditions of this study, no evidence of mutagenic activity was detected for the test substance, Cyclacet, in Salmonella typhimurium test strains TA97a, TA98, TAI00, and TA1535 along with Escherichia coli strain WP2 uvrA (328). The findings of this study show the test substance to be negative for the induction of mutagenicity in the bacterial reverse mutation test.
- Executive summary:
The test substance, Cyclacet, was evaluated in a bacterial reverse mutation assay employing Salmonella typhimurium strains TA97a, TA98, TA100, and TA1535 along with Escherichia coli strain WP2 uvrA (328) both in the presence and absence of an exogenous metabolic activation system. The test substance was evaluated using an initial plate incorporation assay and a confirmatory preincubation procedure.
The solvent, diluent and negative control used in this assay was dimethyl sulfoxide (DMSO). Test substance concentrations of 5, 10, 50, 100, 500, 1000, 2500, and 5000 ug per plate were assessed with respect to negative (solvent) controls in the plate incorporation assay. Due to test article associated toxicity, test substance concentrations were lowered for the confirmatory assay. Concentrations of 5, 10, 50, 100, and 250 ug per plate were assessed with respect to negative (solvent) controls in the confirmatory preincubation assay. In the plate incorporation assay, test substance associated toxicity, as evidenced by a concentration related reduction in the mean number of revertants per plate and/or the reduction of the microcolony background lawns, was observed at 500 ug per plate and above in S. typhimurium tester strains TA97a, TA98, TA100, and TA1535 with and without exogenous metabolic activation along with E. coli strain WP2 uvrA (328) without exogenous metabolic activation. Toxicity was observed at 1000 ug per plate and above in E. coli strain WP2 uvrA (328) with exogenous metabolic activation. Test substance associated precipitate was not observed at any concentration level.
In the preincubation assay, toxicity was observed at 100 ug per plate and above in S. typhimurium test strain TA98 without exogenous metabolic activation and at 250 ug per plate in S. typhimurium strains TA97a, TA100, and TA1535 along with E. coli strain WP2 uvrA (328) without exogenous metabolic activation. No toxicity was observed at the tested concentrations for any strain with exogenous metabolic activation.
The mean number of revertants observed in the negative controls (DMSO) for each of the test strains was within acceptable historical negative control ranges. All test strains demonstrated appropriate phenotypic characteristics.
Under the conditions of this study, no evidence of mutagenic activity was detected for the test substance, Cyclacet, in S. typhimurium test strains TA97a, TA98, TAI00, and TA1535 along with E. coli strain WP2 uvrA (328). The findings of this study show the test substance to be negative for the induction of mutagenicity in the bacterial reverse mutation test.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The information is based on read across
- Justification for type of information:
- Information used for read across to Cyclacet Dihydro. The full read across is documented in the Endpoint summary. The accompanying files are attached below.
Executive summary
Cyclacet Dihydro will have the same result in the Ames test as Cyclacet in view of high similarity in structure: backbone and functional group, which results in a negative result in the Ames test.
Structural similarities and differences: Cyclacet Dihydro, the target, and the source chemical Cyclacet have identical structural features consisting of a tricyclodecan-e/yl fused ring structure and an acetic ester attached at the bridged hexyl ring. The difference is that Cyclacet Dihydro (as presented in the name) does not have a double bond in the pentyl -ring which Cyclacet has.
Toxico-kinetics: The molecular weights, appearance, physic-chemical properties all indicate a similar bioavailability. Metabolism: In both Cyclacet Dihydro and Cyclacet the ester bond will be cleaved by bacteria in the gut and/or enzymes in the liver (Toxicological Handbook). Acetic acid will be one product and the Cyclacet Dihydro- and Cyclacet-alcohol the other metabolite. The parent and the metabolites are very similar and are not expected to have a different toxico-kinetic profile.
Toxico-dynamic: Cyclacet Dihydro and Cyclacet are anticipated to have similar genotoxicity based on their similarity in structure and similar metabolites. The absence of the double bond in Cyclacet Dihydro indicates a lower electrophilicity compared to Cyclacet. In view of this the read across from Cyclacet may be considered conservative.
Uncertainty: There is no uncertainty in the prediction based on the same functional group and very similar backbone. - Reason / purpose for cross-reference:
- read-across source
- Key result
- Species / strain:
- other: S. typhimurium TA97a, TA98, TA100, TA 102, TA1535 and E. coli WP2 uvrA (328)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Cyclacet Dihydro (Cas no 64001-15-6)and its Ames mutagenicity derived from Cyclacet (Cas no generic 54830-99-8)
Introduction
Cyclacet Dihydro has atricyclodecane-fused ring structure to which an acetic-ester is attached (see Data matrix). For this substance no in vitro genemutation in bacteria cells (Ames) information is available. In accordance with Article 13 of REACH, lacking information can be generated by means of applying alternative methods such as in vitro, QSARs, grouping and read-across. For Cyclacet Dihydro the Ames information will be derived from Cyclacet
Hypothesis: Cyclacet Dihydro will have the same result in the Ames test as Cyclacet in view of high similarity in structure: backbone and functional group, which results in a negative result in the Ames test.
Available experimental information: For Cyclacet Dihydro a negative Bluescreen assay is available which is insufficiently covering the REACH requirement. For the analogue Cyclacet a reliable Ames test according to OECD TG 471 study is available (GLP and Klimisch 1) in which no increase in revertants were seen in any of the strains.
Target chemical and source chemical(s)
Chemical structures of the target chemical and the source chemical are shown in the data matrix.
Purity / Impurities
The purity and impurities of the target chemical do not indicate other constituents or impurities (all< 10%) that indicated a different genotoxicity potential.
Analogue approach justification
According to Annex XI 1.5 read across can be used to replace testing when the similarity can be based on a common backbone and a common functional group. When using read across the result derived should be applicable for C&L and/or risk assessment and it should be presented with adequate and reliable documentation.
In accordance with ECHA guidance (2017) Cyclacet is selected as the key source because of the similarities in structure of both substances considering backbone and functional group.
Structural similarities and differences:Cyclacet Dihydro, the target, and the source chemical Cyclacet have identical structural features consisting of a tricyclodecan-e/yl fused ring structure and an acetic ester attached at the bridged hexyl ring. The difference is that Cyclacet Dihydro (as presented in the name) does not have a double bond in the pentyl -ring which Cyclacet has.
Toxico-kinetics: The molecular weights, appearance, physic-chemical properties all indicate a similar bioavailability. Metabolism: In both Cyclacet Dihydro and Cyclacet the ester bond will be cleaved by bacteria in the gut and/or enzymes in the liver (Toxicological Handbook). Acetic acid will be one product and the Cyclacet Dihydro and Cyclacet-alcohol the other metabolite. The parent and the metabolites are very similar and are not expected to have a different toxico-kinetic profile.
Toxico-dynamic:Cyclacet Dihydro and Cyclacet are anticipated to have similar genotoxicity based on their similarity in structure and similar metabolites. The absence of the double bond in Cyclacet Dihydro indicates a lower electrophilicity compared to Cyclacet. In view of this the read across from Cyclacet may be considered conservative.
Uncertainty: There is no uncertainty in the prediction based on the same functional group and very similar backbone. In accordance with ECHA guidance (RAAF, 2017) the read across receives score 5.
Data matrix
The Data matrix is presented below, in Table 1.
Conclusions for acute oral toxicity and classification and labelling
Hazard:The in vitro genotoxicity in bacteria cells of Cyclacet Dihydro is derived from Cyclacet. Cyclacet did not show in vitro genotoxicity in the Ames test and therefore Cyclacet Dihydro is also anticipated to be negative in such a test.
Classification and Labelling: Cyclacet Dihydro does not need to be classified based for in vitro genotoxicity in bacterial cells according to EU CLP (EC 1272/2008 and its amendments).
Table 1: Data matrix presenting the characteristics of Cyclacet Dihydro and its source Cyclacet to support the read across for in vitro genotoxicity in bacterial cells.
Common names |
Cyclacet Dihydro |
Cyclacet |
Chemical structures |
||
|
Target |
Source |
Cas no of the main isomer Cas no of the generic |
64001-15-6 |
2500-83-6 (5-yl) 54830-99-8 |
Einecs |
264-598-7 |
911-369-0 |
REACH registration |
REACH registered for 2018 |
REACH registered |
Empirical formula |
C12H18O2 |
C12H16O2 |
Smiles |
CC(=O)OC3CC1CC3C2CCCC12 |
CC(=O)OC3CC1CC3C2C=CCC12 |
Physico-chemical data |
|
|
Molecular weight |
194 |
192 |
Physical state |
liquid |
liquid |
Vapour pressure Pa (measured) |
2.2 |
2.1 |
Water solubility mg/l (measured) |
89 |
186 |
Log Kow (measured) |
4.5 |
3.9 |
Log Kow (calculated – ECOSAR) |
3.1 |
2.85 |
Human health |
|
|
Ames test |
Read across from Cyclacet |
Negative (OECD TG 471)
|
Justification for classification or non-classification
Cyclacet Dihydro does not need to be classified based on the negative results in the Ames test in accordance with EU CLP (1272/2008 and its amendments)
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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