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EC number: 921-728-3 | CAS number: 64741-66-8
- 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
There is no in vitro genetic toxicity data available for Hydrocarbons, C7-C9, isoalkanes. However, data is available for structural analogues, Hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics and 2,2,4-trimethylpentane and presented in the dossier. This data is read across to Hydrocarbons, C7-C9, isoalkanes based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.
All read across genetic toxicity tests listed below had negative results for Hydrocarbons, C7-C9, isoalkanes.
Genetic Toxicity in vitro - Bacterial reverse mutation assay (OECD 471)
Genetic Toxicity in vitro - Mammalian Chromosome Aberration Test (OECD TG 473)
Genetic Toxicity in vitro - Mammalian Cell Gene Mutation Test (OECD TG 476)
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- September - October 1982
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Test procedure according to national standards
- Justification for type of information:
- The justification for read across is provided as an attachment in IUCLID Section 13.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- - limited documentation of cytotoxicity data
- GLP compliance:
- no
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- S. typhimurium strains: his-operon
E. coli strains: tryptophan-operon - Species / strain / cell type:
- S. typhimurium, other: TA 1535, TA 1537, TA 1538, TA 98, TA 100
- Additional strain / cell type characteristics:
- not specified
- Species / strain / cell type:
- E. coli, other: WP2, WP2 uvr A
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- Rat liver homogenate S9 activation, 10 % S9 liver homogenate from Aroclor treated rats
- Test concentrations with justification for top dose:
- TA 1538 (-S9 mix): 0, 62.5, 125, 250, 500, 1000, 2000, 4000, 8000; (+S9 mix): 0, 62.5, 125, 250, 500, 1000, 2000, 4000, 8000 µg/mL
TA 1538 (-S) mix): 0, 15.62, 31.25, 62.5, 125, 250, 500, 1000; (+S9 mix): 0, 31.25, 62.5, 125, 250, 500, 1000, 2000, 4000, 8000 µg/mL
TA 1537 (-S9 mix): 0, 62.5, 125, 250, 500, 1000, 2000, 4000, 8000; (+S9 mix): 0, 62.5, 125, 250, 500, 1000, 2000, 4000, 8000 µg/mL
TA 1537 (-S9 mix): 0, 3.9, 7.81, 15.62, 31.25, 62.5, 125; (+S9 mix): 0, 31.25, 62.5, 125, 250, 500, 1000, 2000 µg/mL
TA 1535 (-S9 mix): 0, 62.5, 125, 250, 500, 1000, 2000, 4000, 8000; (+S9 mix): 0, 62.5, 125, 250, 500, 1000, 2000, 4000, 8000 µg/mL
TA 100 (-S9 mix): 0, 0.31, 0.62, 1.25, 2.5, 5, 10; (+S9 mix): 0, 7.81, 15.62, 31.25, 62.5, 125, 250 µg/mL
TA 100 (-S9 mix): 0, 31.25, 62.5, 125, 250, 500; (+S9 mix): 0, 62.5, 125, 250, 500, 1000, 2000, 4000, 8000 µg/mL
TA 100 (-S9 mix): 0, 62.5, 125, 250, 500, 1000, 2000, 4000, 8000; (+S9 mix): 0, 62.5, 125, 250, 500, 1000, 2000, 4000, 8000 µg/mL
TA 98 (-S9 mix): 0, 0.31, 0.62, 1.25, 2.5, 5, 10; (+S9 mix): 0, 7.81, 15.62, 31.25, 62.5, 125, 250 µg/mL
TA 98 (-S9 mix): 0, 3.9, 7.81, 15.62, 31.25, 62.5, 125; (+S9 mix): 0, 31.25, 62.5, 125, 250, 500, 1000, 2000 µg/mL
TA 98 (-S9 mix): 0, 62.5, 125, 250, 500, 1000, 2000, 4000, 8000; (+S9 mix): 0, 62.5, 125, 250, 500, 1000, 2000, 4000, 8000 µg/mL
EC WP2 (-S9 mix): 0, 62.5, 125, 250, 500, 1000, 2000, 4000, 8000; (+S9 mix): 0, 62.5, 125, 250, 500, 1000, 2000, 4000, 8000 µg/mL
EC WP2uvrA (-S9 mix): 0, 62.5, 125, 250, 500, 1000, 2000, 4000, 8000; (+S9 mix): 0, 62.5, 125, 250, 500, 1000, 2000, 4000, 8000 µg/mL - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: Tween 80 and ethanol
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- other: TA 1538, TA 98, TA 100: benzo(a)pyrene; TA 1537: neutral red; TA 1535: Sodium azide; and E. coli strains: 4-nitroquinoline-N-oxide
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: preincubation
DURATION
- Preincubation period: 30 min
- Incubation period: 48-72 hours
NUMBER OF REPLICATIONS: All test were carried out in triplicate.
Two replicate assays were carried out on different days to confirm reproducibility of results. - Statistics:
- none
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Remarks:
- Concentrations up to 8000 µg/mL in agar layer cultures did not increase the reverse mutation frequency of S. typhimurium strains either in the presence or absence of a rat liver microsomal activation system.
- Cytotoxicity / choice of top concentrations:
- other: There was a differential toxicity of the test material to individual strains of Salmonella and the reduction of toxicity in the presence of an S9 mix
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Remarks:
- Concentrations up to 8000 µg/mL in agar layer cultures did not increase the reverse mutation frequency of S. typhimurium strains either in the presence or absence of a rat liver microsomal activation system.
- Cytotoxicity / choice of top concentrations:
- other: There was a differential toxicity of the test material to individual strains of Salmonella and the reduction of toxicity in the presence of an S9 mix
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Remarks:
- Concentrations up to 8000 µg/mL in agar layer cultures did not increase the reverse mutation frequency of S. typhimurium strains either in the presence or absence of a rat liver microsomal activation system.
- Cytotoxicity / choice of top concentrations:
- other: There was a differential toxicity of the test material to individual strains of Salmonella and the reduction of toxicity in the presence of an S9 mix
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Remarks:
- Concentrations up to 8000 µg/mL in agar layer cultures did not increase the reverse mutation frequency of S. typhimurium strains either in the presence or absence of a rat liver microsomal activation system.
- Cytotoxicity / choice of top concentrations:
- other: There was a differential toxicity of the test material to individual strains of Salmonella and the reduction of toxicity in the presence of an S9 mix
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Remarks:
- Concentrations up to 8000 µg/mL in agar layer cultures did not increase the reverse mutation frequency of S. typhimurium strains either in the presence or absence of a rat liver microsomal activation system.
- Cytotoxicity / choice of top concentrations:
- other: There was a differential toxicity of the test material to individual strains of Salmonella and the reduction of toxicity in the presence of an S9 mix
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- E. coli WP2 uvr A
- Remarks:
- WP2, WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Remarks:
- Concentrations up to 8000 µg/mL in agar layer cultures did not increase the reverse mutation frequency of E. coli strains either in the presence or absence of a rat liver microsomal activation system
- Cytotoxicity / choice of top concentrations:
- not specified
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- There was no evidence of test compound precipitation in the assay system.
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results:
negative with metabolic activation
negative without metabolic activation
The purpose of this study was to determine the mutagenicity of the test substance hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics. An Ames reverse mutation assay was done on S. typhimurium strains, TA 1535, TA 1537, TA 1538, TA 98 and TA 100, and E. coli strains WP2 uvr A and WP2, both with and without metabolic activation. Species were tested at concentrations ranging from 0.31 to 8000 ug/plate. The test plates were incubated for 48 -72 hrs, and then the number of colonies were counted. For all species, there was no significant increase in the number of revertants as compared to negative controls. Positive controls showed a significant increase in mutations. The test substance is not mutagenic. - Executive summary:
The purpose of this study was to determine the mutagenicity of the test substance hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics. An Ames reverse mutation assay was done on S. typhimurium strains, TA 1535, TA 1537, TA 1538, TA 98 and TA 100, and E. coli strains WP2 uvr A and WP2, both with and without metabolic activation. Species were tested at concentrations ranging from 0.31 to 8000 ug/plate. The test plates were incubated for 48 -72 hrs, and then the number of colonies were counted. For all species, there was no significant increase in the number of revertants as compared to negative controls. Positive controls showed a significant increase in mutations. The test substance is not mutagenic.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- September - October 1982
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Test procedure according to national standards.
- Justification for type of information:
- The justification for read across is provided as an attachment in IUCLID Section 13.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- GLP compliance:
- no
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- mammalian cell line, other: Rat liver epithelial-type line (RL4) cells
- Details on mammalian cell type (if applicable):
- - Type and identity of media: Stock culture media and assay media was Minimal Essential Medium supplemented with 10% fetal calf serum and 1% non-essential amino acids.
- Additional strain / cell type characteristics:
- other: metabolic competent
- Metabolic activation:
- without
- Metabolic activation system:
- RL4 cells are metabolically competent.
- Test concentrations with justification for top dose:
- 0, 2.5, 5.0, and 10 mg/mL
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: Tween 80 and ethanol
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- 7,12-dimethylbenzanthracene
- Details on test system and experimental conditions:
- see "Any other information on materials and methods"
- Key result
- Species / strain:
- mammalian cell line, other: RL4 cells, metabolic competent
- Metabolic activation:
- not applicable
- Genotoxicity:
- negative
- Remarks:
- There was no significant increase in chromosome damage
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Exposure of RL4 cells to 20 µg/mL test substance resulted in inhibition of cell proliferation by 50 %. Therefore final test concentrations of 2.5, 5, and 10 µg/mL were chosen
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- A maximum dose level of 10 µg/mL was determined in the chromosome assay. There was no significant increase beyond control limits in the frequency of chromatid breaks or total chromatid aberrations in rat liver cells exposed to the test material up to 10 µg/mL indicating that the compound did not induce chromosome damage in rat liver cells. A small increase in the percentage of cells showing gaps in exposed cultures was well within historical control ranges. Cultures exposed to the positive control material, DMBA, showed an increase in the frequency of chromosome damage.
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results: negative
This study examined the potential for the test substance, hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics, to cause chromosomal aberrations in rat liver RL4 cells. Cells were exposed to concentrations of 0, 2.5, 5.0, and 10 ug/mL of test substance, and then examined for chromosomal aberrations including polyploidy, chromatid gaps, and chromatid exchanges. The positive control substance was 7,12 -dimethylbenzanthracene. No significant increase in the frequency of chromosomal damage was observed. Based on the study design the test substance showed no genetic toxicity. - Executive summary:
This study examined the potential for the test substance, hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics, to cause chromosomal aberrations in rat liver RL4 cells. Cells were exposed to concentrations of 0, 2.5, 5.0, and 10 ug/mL of test substance, and then examined for chromosomal aberrations including polyploidy, chromatid gaps, and chromatid exchanges. The positive control substance was 7,12 -dimethylbenzanthracene. No significant increase in the frequency of chromosomal damage was observed. Based on the study design the test substance showed no genetic toxicity.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- 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: Acceptable, well documented publication which meets basic scientific principles
- Justification for type of information:
- The justification for read across is provided as an attachment in IUCLID Section 13.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- yes
- Remarks:
- - using microtiter plates
- GLP compliance:
- not specified
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- thymidine kinase
- Species / strain / cell type:
- human lymphoblastoid cells (TK6)
- Details on mammalian cell type (if applicable):
- - Type and identity of media: RPMI 1640 medium supplemented with 15% heat-inactivated horse serum
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- with Aroclor induced-rat liver homogenate
- Test concentrations with justification for top dose:
- 5 % v/v TMP in DMEM medium, administered undiluted or as 50 % (1:1 saturated to normal medium)
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMEM medium
- Untreated negative controls:
- yes
- Remarks:
- with and without S9
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMEM medium
- Positive controls:
- yes
- Remarks:
- for S9 activated cultures
- Positive control substance:
- benzo(a)pyrene
- Remarks:
- Migrated to IUCLID6: 15 µM
- Untreated negative controls:
- yes
- Remarks:
- with and without S9
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMEM medium
- Positive controls:
- yes
- Remarks:
- for non-activated cultures
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- Migrated to IUCLID6: 0.2 mM
- Details on test system and experimental conditions:
- see "any other information on materials and methods"
- Key result
- Species / strain:
- human lymphoblastoid cells (TK6)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Remarks:
- TMP did not induce significant increases in the mutation frequency at the thymidine kinase locus.
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Cell survival in TMP-saturated medium with and without metabolic activation was greater than 50-60 %.
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Additional information on results:
- The elevated mutation frequencies of positive control compounds were as expected.
ADDITIONAL INFORMATION ON CYTOTOXICITY:
Cell survival in positive control treated cultures was 40 or 30% for benzo(a)pyrene and EMS, respectively - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results: negative
Based on the study design there is no incidence of increased genetic toxicity caused by the test substance. - Executive summary:
Based on the study design there is no incidence of increased genetic toxicity caused by the test substance.
Referenceopen allclose all
Table: Relative Mutation Rate – Bacterial Experiment I without Metabolic Activation
Concentration |
E. coli WP2 |
E. coli WP2 uvr A |
S. typhimurium TA 1535 |
S. typhimurium TA 1537 |
S. typhimurium TA 1538 |
S. typhimurium TA 98 |
S. typhimurium TA 100 |
Without S9 |
|||||||
3.91 |
- |
- |
- |
- |
- |
- |
- |
7.81 |
- |
- |
- |
- |
- |
- |
- |
15.6 |
- |
- |
- |
- |
- |
- |
- |
31.3 |
- |
- |
- |
- |
- |
- |
- |
62.5 |
0.8 |
0.7 |
1.2 |
0.1 |
0.7 |
0.2 |
1.4 |
125 |
0.9 |
0.6 |
0.7 |
0 |
0.4 |
0 |
0.7 |
250 |
0.7 |
0.8 |
0.6 |
0 |
0 |
0 |
0.3 |
500 |
0.7 |
0.7 |
0.9 |
0 |
0 |
0 |
0.1 |
1000 |
0.8 |
0.5 |
0.9 |
0 |
0 |
0 |
0 |
2000 |
0.7 |
0.6 |
0.7 |
0 |
0 |
0 |
0 |
4000 |
0.8 |
0.6 |
0.6 |
0 |
0 |
0 |
0 |
8000 |
0.6 |
0.5 |
0.7 |
0 |
0 |
0 |
0 |
Sodium azide 2 µg |
- |
- |
89.8 |
- |
- |
- |
- |
Benzo(a)-pyrene 7 µg |
- |
- |
- |
- |
1.0 |
0.7 |
0.9 |
4-nitroquinoline-N-oxide 3 µg |
39.8 |
3.2 |
- |
- |
- |
- |
- |
Neutral red 7 µg |
- |
- |
- |
1.8 |
- |
- |
- |
Table: Relative Mutation Rate – Bacterial Experiment I with Metabolic Activation
Concentration |
E. coli WP2 |
E. coli WP2 uvr A |
S. typhimurium TA 1535 |
S. typhimurium TA 1537 |
S. typhimurium TA 1538 |
S. typhimurium TA 98 |
S. typhimurium TA 100 |
Without S9 |
|||||||
31.3 |
- |
- |
- |
- |
- |
- |
- |
62.5 |
0.7 |
1.3 |
1.4 |
0.3 |
1.5 |
0.7 |
1.0 |
125 |
0.8 |
1.0 |
1.1 |
0.2 |
1.3 |
1.3 |
0.8 |
250 |
0.9 |
1.0 |
0.8 |
0.6 |
1.5 |
1.2 |
1.0 |
500 |
0.7 |
0.8 |
1.0 |
0.2 |
1.0 |
0.7 |
1.3 |
1000 |
0.7 |
0.7 |
1.0 |
0.4 |
0.7 |
0.2 |
1.4 |
2000 |
1.1 |
0.9 |
1.1 |
0 |
0.4 |
0 |
1.2 |
4000 |
1.0 |
1.0 |
1.0 |
0 |
0.7 |
0 |
1.1 |
8000 |
0.8 |
1.0 |
0.5 |
0 |
0.7 |
0 |
1.1 |
Sodium azide 2 µg |
- |
- |
15.2 |
- |
- |
- |
- |
Benzo(a)-pyrene 7 µg |
- |
- |
- |
- |
3.7 |
5.3 |
3.1 |
4-nitroquinoline-N-oxide 3 µg |
1.2 |
3.6 |
- |
- |
- |
- |
- |
Neutral red 7 µg |
- |
- |
- |
4.4 |
- |
- |
- |
Table: Relative Mutation Rate – Bacterial Experiment II without Metabolic Activation
Concentration |
E. coli WP2 |
E. coli WP2 uvr A |
S. typhimurium TA 1535 |
S. typhimurium TA 1537 |
S. typhimurium TA 1538 |
S. typhimurium TA 98 |
S. typhimurium TA 100 |
Without S9 |
|||||||
3.91 |
- |
- |
- |
1.1 |
- |
0.8 |
- |
7.81 |
- |
- |
- |
0.6 |
- |
0.9 |
- |
15.6 |
- |
- |
- |
0.7 |
0.9 |
0.8 |
- |
31.3 |
- |
- |
- |
0.4 |
1.0 |
0.8 |
1.1 |
62.5 |
1.0 |
1.0 |
1.2 |
0.4 |
0.7 |
0.4 |
1.0 |
125 |
1.0 |
1.0 |
0.9 |
0 |
0.5 |
0 |
0.9 |
250 |
0.7 |
0.8 |
1.4 |
- |
0.2 |
- |
1.0 |
500 |
0.9 |
0.7 |
1.1 |
- |
0 |
- |
0.7 |
1000 |
1.0 |
0.8 |
0.9 |
- |
0 |
- |
- |
2000 |
0.7 |
0.9 |
0.7 |
- |
- |
- |
- |
4000 |
0.9 |
0.8 |
0.9 |
- |
- |
- |
- |
8000 |
0.8 |
0.7 |
0.9 |
- |
- |
- |
- |
Sodium azide 2 µg |
- |
- |
86.6 |
- |
- |
- |
- |
Benzo(a)-pyrene 7 µg |
- |
- |
- |
- |
1.1 |
1.1 |
1.3 |
4-nitroquinoline-N-oxide 3 µg |
36.7 |
5.3 |
- |
- |
- |
- |
- |
Neutral red 7 µg |
- |
- |
- |
1.2 |
- |
- |
- |
Table: Relative Mutation Rate – Bacterial Experiment II with Metabolic Activation
Concentration |
E. coli WP2 |
E. coli WP2 uvr A |
S. typhimurium TA 1535 |
S. typhimurium TA 1537 |
S. typhimurium TA 1538 |
S. typhimurium TA 98 |
S. typhimurium TA 100 |
Without S9 |
|||||||
31.3 |
- |
- |
- |
1.1 |
0.9 |
0.8 |
- |
62.5 |
0.9 |
0.9 |
0.7 |
1.2 |
1.1 |
1.0 |
1.1 |
125 |
1.1 |
1.0 |
1.2 |
1.1 |
1.1 |
0.9 |
1.0 |
250 |
1.4 |
0.8 |
0.8 |
1.4 |
1.1 |
0.8 |
1.1 |
500 |
1.2 |
1.0 |
0.9 |
1.0 |
1.1 |
0.8 |
1.2 |
1000 |
1.0 |
1.1 |
0.8 |
0.5 |
0.9 |
0.4 |
0.9 |
2000 |
0.8 |
1.0 |
1.1 |
0 |
0.9 |
0.1 |
0.9 |
4000 |
0.8 |
0.9 |
0.8 |
- |
0.5 |
- |
0.9 |
8000 |
1.0 |
0.7 |
0.7 |
- |
0.4 |
- |
0.9 |
Sodium azide 2 µg |
- |
- |
18.2 |
- |
- |
- |
- |
Benzo(a)-pyrene 7 µg |
- |
- |
- |
- |
9.7 |
6.1 |
6.5 |
4-nitroquinoline-N-oxide 3 µg |
1.1 |
2.8 |
- |
- |
- |
- |
- |
Neutral red 7 µg |
- |
- |
- |
5.2 |
- |
- |
- |
Table: Metaphase chromosome analysis of RL4cells
0 µg/ml |
2.5 µg/ml |
5.0 µg/ml |
10.0 µg/ml |
1.0 µg/ml 7,12-dimethylbenzanthracene |
|
Polyploidy (% cells) |
1.3 |
1.3 |
1.3 |
1.3 |
0.5 |
Chromatid gaps (% cells) |
0.3 |
0.7 |
0.9 |
1.0 |
5.5 |
Multiple aberrations (% cells) |
- |
- |
- |
- |
- |
Severe damage (% cells) |
- |
- |
- |
- |
- |
Chromatid aberrations (% cells) |
0.7 |
- |
0.9 |
- |
4.0 |
Chromosome aberrations (% cells) |
- |
- |
- |
- |
1.5 |
Chromatid gaps (frequency per cell) |
0.003 |
0.007 |
0.009 |
0.010 |
0.060 |
Chromatid breaks (frequency per cell) |
0.007 |
- |
0.004 |
- |
- |
Chromatid exchange (frequency per cell) |
- |
- |
0.004 |
- |
- |
Chromosome breaks (frequency per cell) |
- |
- |
- |
- |
0.015 |
Chromosome exchange (frequency per cell) |
- |
- |
- |
- |
- |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
In vivo genetic toxicity data is
available for Hydrocarbons, C7-C9, isoalkanes.
Hydrocarbons,
C7-C9, isoalkanes was not mutagenic in the rodent dominant lethal test.
Link to relevant study records
- Endpoint:
- in vivo mammalian germ cell study: cytogenicity / chromosome aberration
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- July 1978 - January 1980
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline with acceptable restrictions.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test)
- Principles of method if other than guideline:
- Similar to OECD 478, only two dose levels were used.
- GLP compliance:
- not specified
- Type of assay:
- rodent dominant lethal assay
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, Massachusetts
- Age at study initiation: males: 10 weeks at initiation of pre-treatment mating period; females: 9 weeks at initiation of week 1 of pre-treatment mating period; females: 8 weeks at initiation of week 1 of post-treatment mating period
- Housing: males: individually housing during the treatment period; females: individually housing during the pre- and post-mating period
- Diet: Purina Laboratory Chow; ad libitum; except chamber-exposed groups during the treatment period
- Water: ad libitum; except chamber-exposed groups during the treatment period
- Route of administration:
- inhalation
- Vehicle:
- none
- Details on exposure:
- TYPE OF INHALATION EXPOSURE: whole body
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The stainless steel and glass chambers had a total volume of one cubic metre with an effective volume of 760 L.
- Air flow rate: 132 L/min
- Air change rate: every 7.6 min
- The test substance was placed in fritted-bottom, gas-washing bottles. Dry air, at various flow rates, was passed through the test material and the vapour-air mixtures entered the chamber air inlets and were further diluted with room air to provide the desired concentrations.
TEST ATMOSPHERE
Atmospheric sampling was performed using a Wilks Scientific Corp., Miran IA Ambient Air Analyzer (long pathlength infrared). On each exposure day three samples were drawn from each exposure chamber (at 1, 3 and 5 hours) and the exposure concentrations calculated by comparing the absorption of this sample to the standard curve. - Duration of treatment / exposure:
- 8 consecutive weeks
- Frequency of treatment:
- 6 hours/day, 5 days/week
- Post exposure period:
- 4 weeks
- Remarks:
- Doses / Concentrations:
400 and 1200 ppm
Basis:
nominal conc. - No. of animals per sex per dose:
- only males were exposed: 10/group
- Control animals:
- yes, sham-exposed
- Positive control(s):
- triethylenemelamine
- Route of administration: intraperitoneally on a single day, at least 2 hours prior to mating
- Doses level/ volume: 0.5 mg/kg body weight; 1 mL/kg body weight
- Vehicle: 0.9 % injectable normal saline solution - Tissues and cell types examined:
- Males: testes, seminal vesicles, epididymides, prostate tissues
Females: uteri - Details of tissue and slide preparation:
- METHOD OF ANALYSIS:
Males: Seminal vesicles, epididymides, prostate and any abnormal lesion or tissue masses were preserved in 10 % neutral buffered formalin. Testes were stored for 48 hours in Bouin´s solution and subsequently placed in formalin. Tissues from 5 randomly chosen males from each group were examined.
Females: The uteri from all females (pregnant and non-pregnant) were appropriately identified and preserved intact in a 10 % neutral buffered formalin solution. - Statistics:
- Comparisons were made during the treatment and post-treatment periods between negative control, positive control and test substance-treated groups by the Chi-square test. Absolute data were compared by using the F-test and Student´s t-test. When variances differed significantly, Student´s t-test was appropriately modified using Cochran´s approximation (t´). Corpora lutea and implantation data were evaluated by the one-tailed test.
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Remarks:
- At dose level of 400 and 1200 ppm the test substance was not mutagenic in rats by the dominant-lethal test.
- Toxicity:
- no effects
- Vehicle controls validity:
- other: no vehicle was used
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- Interpretation of results: negative
Under the conditions of the test no negative effects were induced by the test substance, hydrocarbons, C7-C9, isoalkanes. - Executive summary:
Under the conditions of the test no negative effects were induced by the test substance, hydrocarbons, C7 -C9, isoalkanes.
Reference
No treatment-related effects were observed for mortality, in-life physical or necropsy examinations and for body weights in males.
No treatment effect was indicated from microscopic evaluation of testes, seminal vesicles, epididymides and prostate tissues from 5 randomly chosen males from each exposure group.
In one animal of the 400 ppm exposure group a caseous mass was observed in the left epididymis. This caseous mass was seen microscopically to be a spermatic granuloma. Since this was observed in a single animal, this is not considered to be treatment related. Several animals (one in control, one in 100 ppm group, one in 1200 ppm group) presented a purulent prostatitis which was of probable bacterial etiology.
Pregnancy rates, implantation data and implantation efficiency values and fetal death data for females mated to treated males were considered comparable to data for females mated to negative control males for each week of the post-treatment mating period. At dose level of 400 and 1200 ppm the test substance was not mutagenic in rats by the dominant-lethal test.
Positive control:
Females mated to the positive control males had fewer implants and lower implantation efficiency values (indicative of pre-implantation loss) than females mated to the negative control males. Fetal death parameters (mean and expressed as a percentage of total implants) for these same females were significantly increased during the post-treatment mating interval.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
While in vivo genetic toxicity data is available, there is no in vitro genetic toxicity data available for Hydrocarbons, C7-C9, isoalkanes. However, in vitro genetic toxicity data is available for structural analogues, Hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics; and 2,2,4-trimethylpentane (Iso-octane) and presented in the dossier. This data is read across to Hydrocarbons, C7-C9, isoalkanes based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.
In vitro
In Vitro gene mutation study in bacteria
Hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics
A reliable bacterial reverse mutation assay (Ames test) was conducted with hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics following a protocol similar to OECD 471 (Shell, 1983).The pre-incubation procedure was performed with Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100, and Escherichia coli strains WP2 uvr A and WP2. The strains were exposed to concentrations ranging from 0.31 to 8000 µg/plate for 30 min both with and without metabolic activation prior to plating and further incubation for 48 -72 h. For all strains tested, there was no significant increase in the number of revertants as compared to negative controls. An initial cytotoxicity assay with S. typhimurium TA100 showed that the test substance was extremely cytotoxic, especially in the absence of S9 fraction. Therefore, initial mutation assays were conducted over a low dose range (0.31 -10 µg per mL) with strains TA100 and TA98. Virtually no cytotoxicity was observed at these concentrations, and so more appropriate concentrations were tested for all strains in subsequent assays. Salmonella strains were more sensitive to the cytotoxic effect of the test substance than E. coli strains, and cytotoxicity was greater in the absence of S9-fraction. In conclusion, the test substance was not mutagenic in this assay (Shell Chemicals, 1983; Brooks et al., 1988).
In Vitro Chromosome Aberration in Mammalian Cells
Hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics
The potential of hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics to cause chromosomal aberrations in rat liver RL4 cells was tested with a method comparable to OECD 473. Cells were exposed to concentrations of 0, 2.5, 5, and 10 µg/mL of test substance for 22 h, and then examined for chromosomal aberrations including polyploidy, chromatid gaps, and chromatid exchanges. Exposure of RL4 cells to 20 µg/mL test substance resulted in inhibition of cell proliferation by 50%. Therefore 10 µg/mL was chosen as the maximum dose level. No significant increase in the frequency of chromosomal damage was observed. Under the conditions of this study, the test material was not clastogenic (Shell Chemicals, 1983; Brooks et al., 1988).
In Vitro Gene Mutation study in Mammalian Cells
2,2,4-trimethylpentane
2,2,4-trimethylpentane (Iso-octane; CAS No. 540-84-1) was tested in a mammalian cell gene mutation assay performed according to OECD 476. The test material was prepared by adding iso-octane at a final concentration of 5 % v/v in culture (DMEM) medium and stirred overnight at room temperature in a foil wrapped, capped parafilm-sealed bottle to saturate the medium. Human lymphoblastoid cells (TK6) were exposed to 100 or 50 % of this saturated DMEM medium with and without metabolic activation for 3 h and allowed for expression for 4 to 8 days. Both with and without metabolic activation, iso-octane did not induce significant increases in the mutation frequency at the thymidine kinase locus and cell survival in iso-octane saturated medium was greater than 50-60 %. Based on the study design there was no incidence of increased genetic toxicity caused by the test substance (Richardson et al., 1986).
In Vivo
Hydrocarbons, C7-C9, isoalkanes
Hydrocarbons, C7-C9, isoalkanes tested in a dominant lethal study (similar to OECD 478) showed no evidence of genotoxicity in the germ cells of treated male rats exposed to 400 or 1200 ppm by inhalation (ExxonMobil Chemical,1980).
The in vivo genotoxicity of other analogues has been tested. Hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics were not clastogenic to mouse bone marrow cells. Iso-octane did not induce unscheduled DNA synthesis in rat hepatocyte cultures. Based on an analogue approach, these results suggest that hydrocarbons, C7-C9, isoalkanes are not expected to induce genotoxicity in vivo.
Justification for classification or non-classification
The negative results in read across in vitro and substance specific in vivo genotoxicity assays do not warrant the classification of Hydrocarbons, C7-C9, isoalkanes as genotoxic under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).
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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