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EC number: 603-501-8 | CAS number: 13171-18-1
- 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 gene mutation study in bacteria
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH : It is hypothesized that the results of an ames assay will be the same for substances that share common structural fragments and functional groups. This principle is explained in detail in Benigni, R. & Bossa, C. (2011). Mechanisms of chemical carcinogenicity and mutagenicity: a review with implications for predictive toxicology. Chem. Revs. 111, 2507-2536 and Benigni, R., Bossa C., Tcheremenskaia O. (2013) In vitro cell transformation assays for an integrated, alternative assessment of carcinogenicity: a data-based analysis. Mutagenesis 2013;28(1):107-16.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES) : Both the target and source chemicals are very high purity substances (>99.99%). The source chemical is used as a surgical anesthetic. The target chemical is a precursor and metabolite of the source chemical.
3. ANALOGUE APPROACH JUSTIFICATION : The target substance is structurally identical to the source substance except the target substance is a hexafluromethoxypropane and the source substance is a heptafluorooxypropane, neither of which contain any structural alerts for mutagenicity in the ames assay according to the model developed by Istituto Superiore di Sanita for the EC Joint Research Centre, Computational Toxicology and IdeaConsult Ltd. Sofia, Bulgaria available in Toxtree (Estimation of Toxic Hazard - A Decision Tree Approach) v3.1.0-1851-1525442531402. This model is reported in Benigni, R. & Bossa, C. (2011). Mechanisms of chemical carcinogenicity and mutagenicity: a review with implications for predictive toxicology. Chem. Revs. 111, 2507-2536 and Benigni, R., Bossa C., Tcheremenskaia O. (2013) In vitro cell transformation assays for an integrated, alternative assessment of carcinogenicity: a data-based analysis. Mutagenesis 2013;28(1):107-16. In addition, both the target and source substance are expected to be absorbed, distributed, metabolized, and excreted similarly in vivo with Cytochrome P450 2E1 expected to be the major isoform responsible for oxidative metabolism of both substances. In animal studies, 95% of inhaled Sevoflurane (source substance) was expired unchanged. Therefore, the structural differences are not expected to impact the results of the Ames test.
4. DATA MATRIX: The target and source substances are nearly identical in terms of molecular weight, physical state, boiling point, specific gravity, vapor pressure, water solubility, and octanol-water partition coefficient.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- read-across source
Reference
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- Not Reported
- 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)
- Deviations:
- yes
- Remarks:
- Only strains TA1535 and TA100 tested
- Principles of method if other than guideline:
- Bacteria were exposed to using a direct plate method, using sealed containers, and by exposure to the vapor. Each test consisted of 6 replicates.
- GLP compliance:
- no
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- Reported as: Sevoflurane; CH2F-O-CH(CF3)2
- Species / strain / cell type:
- S. typhimurium TA 1535
- Species / strain / cell type:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Metabolic activation system:
- Rat Liver (S9)
- Test concentrations with justification for top dose:
- Vapor: 0.1%, 1%, 2%, 10%, 20%, and 30% by volume for 8 hours.
Direct Plate: 1, 10, and 30 ul/plate. - Vehicle / solvent:
- Vapor testing: Air was the vehicle.
Direct Plate: None - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- no
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: Vinylidene Chloride (3%)
- Details on test system and experimental conditions:
- Vapor Testing: Bacteria on petri plates were exposed to test anesthetic vapor for 8 hours in desiccators.
Direct Plate: Liquid anesthetic was added to soft agar and bacteria, and the mixture was spread on histidine-deficient culture medium. - Rationale for test conditions:
- Not Reported.
- Evaluation criteria:
- Number of revertants per plate.
- Statistics:
- Methods Not Reported.
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Conclusions:
- The read-across substance, Sevoflurane, was not mutagenic in the Ames test when bacterial strains TA1535 or TA100 were exposed with or without metabolic activation to vapor or when exposed directly to the liquid.
- Executive summary:
In a non-GLP study conducted in a manor similar to OECD 471 (Bacterial Reverse Mutation Assay) using bacterial strains TA1535 and TA100 only, the vapor and liquid of the test substance (Sevoflurane) was not mutagenic with or without metabolic activation.
Vapor Test w/S9 Activation: Number of Revertants per Plate ( ±SD)
Strain |
Control Air |
Vapor Percent (v/v) (Desiccator) |
|||||
0.1 |
1 |
2 |
10 |
20 |
30 |
||
TA1535 |
23 ±3 |
27 ± 3 |
26 ± 7 |
20 ± 2 |
23 ± 3 |
16 ± 1 |
15 ± 2 |
TA100 |
128 ±7 |
141 ± 9 |
145 ± 11 |
124 ± 3 |
124 ± 23 |
130 ± 33 |
150 ± 12 |
Direct Plate w/S9 Activation: Number of Revertants per Plate ( ±SD)
Strain |
Control Air |
µl/Plate (Direct Plate) |
Positive Control |
||
1 |
10 |
30 |
|||
TA1535 |
23+/- 3 |
15 ± 2 |
13 ± 4 |
11 ± 3 |
69 ± 5 |
TA100 |
128+/-7 |
100 ± 12 |
121 ± 15 |
100 ± 10 |
415 ± 25 |
- Reason / purpose for cross-reference:
- read-across: supporting information
Reference
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Study period:
- 18 May 2019
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
- Justification for type of information:
- 1. SOFTWARE
: Toxtree (Estimation of Toxic Hazard - A Decision Tree Approach)
2. MODEL (incl. version number) : In vitro mutagenicity (Ames test) alerts by ISS available in Toxtree (Estimation of Toxic Hazard - A Decision Tree Approach) v3.1.0-1851-1525442531402
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL : COC(C(F)(F)F)C(F)(F)F
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL: The model was developed by Istituto Superiore di Sanita for the EC Joint Research Centre, Computational Toxicology and IdeaConsult Ltd. Sofia, Bulgaria. The basis of the model are explained in detail in Benigni, R. & Bossa, C. (2011). Mechanisms of chemical carcinogenicity and mutagenicity: a review with implications for predictive toxicology. Chem. Revs. 111, 2507-2536. and Benigni, R., Bossa C., Tcheremenskaia O. (2013) In vitro cell transformation assays for an integrated, alternative assessment of carcinogenicity: a data-based analysis. Mutagenesis 2013;28(1):107-16. This model is included in the OECD QSAR Toolbox.
5. APPLICABILITY DOMAIN : The model assesses the chemical's structure and identifies any fragraments or functional groups that have been associated with mutagenicity in the Ames assay. Since this substance contains no unusual elements or functional groups, only C, CH, CH3, O, and F, the substance can be presumed to fit within the models domain.
6. ADEQUACY OF THE RESULT: The SAR model found no structural alerts for mutagenicity in the Ames assay. This result is as expected and is supported by measured data on a similar substance, Sevoflurane, which was negative in the Ames assay with and without metabolic activation. - Qualifier:
- no guideline required
- Principles of method if other than guideline:
- Accepted SAR Model Toxtree Module: In vitro mutagenicity (Ames test) alerts by ISS available in Toxtree (Estimation of Toxic Hazard - A Decision Tree Approach) v3.1.0-1851-1525442531402.
- GLP compliance:
- no
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- SMILES Used: COC(C(F)(F)F)C(F)(F)F
- Key result
- Species / strain:
- other: All Common Strains used in Ames Assay
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not determined
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- not applicable
- Remarks on result:
- no mutagenic potential (based on QSAR/QSPR prediction)
- Conclusions:
- The substance does not contain any fragrments or functional groups commonly associated with mutagenicity in the Ames Assay.
- Executive summary:
In a Structural Activity Relationships (SAR) assessment of mutagenicity using the software "In vitro mutagenicity (Ames test) alerts by ISS" available in Toxtree (Estimation of Toxic Hazard - A Decision Tree Approach) v3.1.0-1851-1525442531402, there were no structural alerts identified for the substance. It can therefore be concluded that the substance is unlikely to be mutagenic in the Ames Assay. This result is supported by measured data on a similar substance, Sevoflurane, which was negative in the Ames assay with and without metabolic activation.
Data source
Materials and methods
Test material
- Reference substance name:
- 1,1,1,3,3,3-hexafluoro-2-methoxypropane
- Cas Number:
- 13171-18-1
- Molecular formula:
- C4-H4-F6-O
- IUPAC Name:
- 1,1,1,3,3,3-hexafluoro-2-methoxypropane
- Test material form:
- liquid: volatile
Constituent 1
Results and discussion
Test resultsopen allclose all
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
Applicant's summary and conclusion
- Conclusions:
- The substance is not expected to be mutagenic in the Ames test based on read-across to the closely related analog substance Sevoflurane which is used as a surgical anesthetic.
- Executive summary:
The substance is not expected to be mutagenic in the Ames test based on read-across to the closely related analog substance Sevoflurane which is used as a surgical anesthetic.
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