Registration Dossier
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EC number: 246-805-2 | CAS number: 25306-75-6
- 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
There are conclusive but not suffcient data for the classification of substance SIBX with regard to mutagenicity/genetic toxicity. It is concluded that the substance SIBX does not meet the criteria to be classified for human health hazards for Mutagenicity-Genetic Toxicity
Link to relevant study records
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- 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
- Justification for type of information:
- 2-methylpropan-1-ol /Isobutyl alcohol/ is both reagents used in the manufacture of sodium O-isobutyl dithiocarbonate . Therefore, 2-methylpropan-1-ol /Isobutyl alcohol/ need to be considered in the assessment of sodium O-isobutyl dithiocarbonate.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Principles of method if other than guideline:
- Clastogenic effects were studied by the micronucleus test using the Chinese hamster V79 cell line as a target.
- GLP compliance:
- not specified
- Type of assay:
- in vitro mammalian cell micronucleus test
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- - Type and identity of media: MEM Eagle medium (V79 cells) supplemented with 10% heat-inactivated fetal calf serum (FCS), 2 mM L-glutamine,
100 IU/ml penicillin and streptomycin.
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: no data
- Periodically checked for karyotype stability: no data
- Periodically "cleansed" against high spontaneous background: no data - Metabolic activation:
- without
- Test concentrations with justification for top dose:
- 11 and 53 mM
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: [no data]
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 4 hours at 37 °C
- Expression time (cells in growth medium): additional 24 hours
NUMBER OF CELLS EVALUATED: 1000 cells/culture
DETERMINATION OF CYTOTOXICITY
- Method: relative total growth - Evaluation criteria:
- The test compound was classified as a clastogen when it was able to enhance the spontaneous MN frequency at least three-fold or higher over that of the control for at least one dose tested.
- Statistics:
- no data
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- No mutagenic activity of Isobutyl Alcohol detected.Isobutyl Alcohol is both reagents used in the manufacture, as well as decomposition products of Sodium isobutyl xanthate. Therefore, the health effects of Isobutyl Alcohol need to be considered in the assessment of sodium isobutyl xanthate. In addition, xanthates decompose on aging to form a number of byproducts, depending on the pH, temperature, etc. Risks associated with xanthate are, therefore, a function of the breakdown of the product or un-reacted raw materials remaining in the product.
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results:negative
No mutagenic activity of Isobutyl Alcohol detected. 2-methylpropan-1-ol /Isobutyl alcohol/ is both reagents used in the manufacture of sodium O-isobutyl dithiocarbonate. Therefore, 2-methylpropan-1-ol /Isobutyl alcohol/ need to be considered in the assessment of sodium O-isobutyl dithiocarbonate - Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- other: published data
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. SIBX readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of SIBX. In addition, xanthates decompose on aging to form a number of byproducts, depending on the pH, temperature, etc. Risks associated with xanthate are, therefore, a function of the breakdown of the product or un-reacted raw materials remaining in the product.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OTS 798.5265 (The Salmonella typhimurium Bacterial Reverse Mutation Test)
- Deviations:
- no
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix- rat liver, Aroclor 1254 administered
- Test concentrations with justification for top dose:
- 0.005%, 0.01%, 0.025%, 0.05%, 0.1% v/v
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: none
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- no
- Remarks:
- no solvent/vehicle used
- Positive controls:
- yes
- Positive control substance:
- other: in the abscence and presence of metabolic activation: 2-aminoanthracene (TA1535), benzo[alpha]pyrene (TA1537, TA100, TA98); in the abscence of metabolic activation: sodium azide (TA1535, TA100), 9-aminoacridine (TA1537), 2-nitrofluorene (TA98);
- Remarks:
- dicloromethane in a vapour phase (7.5% v/v) was included in each test without metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
NUMBER OF REPLICATIONS:3/ treatment
DETERMINATION OF CYTOTOXICITY
- Method: abscence or thinning of the background lawn of non-revertant colonies
EXPOSURE TO CS2:
Sets of solidified plates were placed, with lids removed, in stainless steel racks, designed to keep the plates separate and permit atmospheric circulation, inside stainless steel vessels. These vessels were then sealed and partially evacuated. Calculated volumes of carbon disulphide liquid were injected into the vessels via a septum and allowed to vaporize, producing atmospheres containing carbon disulphide at the nominal concentrations
mentioned above.Sterile air was admitted to the vessels in order to equilibrate the contents to atmospheric pressure, and the vessels with their contents were incubated at 37°C for 48 hours. After removal from the vessels, the plates were incubated for a further day in order to permit revertant
colonies to grow to a size large enough to be scored. - Evaluation criteria:
- number of revertants/plate
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other: yes, only at the highest concentration
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other: yes, only at the highest concentration
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other: yes, only at the highest concentration
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other: yes, only at the highest concentration
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other: yes, only at the highest concentration
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Carbon disulphide was examined for its mutagenic activity in four histidine-dependent auxotrophs ofSalmonella typhimurium, strains TA98, TA100, TA1535, TA1537, TA102. Agar plates, seeded with the tester strains, were exposed to the test material in vapour phase, in the abscence and presence of metabolic activation, in the following nominal concentrations: 0.005%, 0.01%, 0.025%, 0.05% and 0.1% v/v (nominal). These concentrations were selected following preliminary toxicity tests in strain TA 98. Carbon disulphide did not exhibit any mutagenic activity under the conditions of this test. No increases in revertants were obtained in any of the four tester strains following exposure to carbon disulphide at the concentrations tested. Inhibition of bacterial growth, observed as thinning of the background lawn of non-revertant cells and reduction in revertant colony numbers, occurred in all strains with carbon disulphide at a nominal concentration of 0.1 % v/v. The positive and negative controls were valid.
The study was performed according to the OECD Guidelines for Testing of Chemicals No. 471 (1983) and US EPA (TSCA) Guideline § 798.5265 (1985, amended 1987). - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results:negative
No mutagenic activity of CS2 detected.Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. SIBXreadily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of SIBX.
In addition, xanthates decompose on aging to form a number of byproducts, depending on the pH, temperature, etc. Risks associated with xanthate are, therefore, a function of the breakdown of the product or un-reacted raw materials remaining in the product. - Executive summary:
Carbon disulphide was examined for its mutagenic activity in four histidine-dependent auxotrophs of Salmonella typhimurium, strains TA98, TA100, TA1535, TA1537, TA 102. Agar plates, seeded with the tester strains, were exposed to the test material in vapour phase, in the abscence and presence of metabolic activation, in the following nominal concentrations: 0.005%, 0.01%, 0.025%, 0.05% and 0.1% v/v (nominal). These concentrations were selected following preliminary toxicity tests in strain TA 98. Carbon disulphide did not exhibit any mutagenic activity under the conditions of this test. No increases in revertants were obtained in any of the four tester strains following exposure to carbon disulphide at the concentrations tested. Inhibition of bacterial growth, observed as thinning of the background lawn of non-revertant cells and reduction in revertant colony numbers, occurred in all strains with carbon disulphide at a nominal concentration of 0.1 % v/v. The positive and negative controls were valid. The study was performed according to the OECD Guidelines for Testing of Chemicals No. 471 (1983) and US EPA (TSCA) Guideline § 798.5265 (1985, amended 1987).
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- 2-methylpropan-1-ol /Isobutyl alcohol/ is both reagents used in the manufacture of sodium O-isobutyl dithiocarbonate . Therefore, 2-methylpropan-1-ol /Isobutyl alcohol/ need to be considered in the assessment of sodium O-isobutyl dithiocarbonate
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Principles of method if other than guideline:
- The mutagenicity of the test chemical was examined in Salmonella typhimurium (TA98, TA100, TA1535, TA1537, and TA1538) and Escherichia coli (WP2uvrA) using the preincubation method with and without S9 mix.
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium, other: TA98, TA100, TA1535, TA1537, and TA1538
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- S-9 mix
- Test concentrations with justification for top dose:
- 5; 10; 50; 100; 500; 1000; 5000 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: [water]
- Justification for choice of solvent/vehicle: none given - Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: TA98, TA100 and E.coli WP2 uvrA:2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide; TA1535: N-ethyl-N-nitro-N-nitrosoguanidine; TA1537: 9-aminoacridine; TA1538: 4-nitroquinoline-N-oxide
- Remarks:
- without S-9 mix
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: TA100, TA98, TA1537 and TA1538: benzo(a)pyrene; TA1535 and E.coli WP2 uvrA: 2-aminoanthracene
- Remarks:
- with S-9 mix
- Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation
DURATION
- Preincubation period: 20 min at 37 °c
- Exposure duration: 2 days at 37 °C
DETERMINATION OF CYTOTOXICITY
- Method: relative total growth- Evaluation criteria:
- no data
- Statistics:
- no data
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- not valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- No mutagenic activity of Isobutyl Alcohol detected.Isobutyl Alcohol is both reagents used in the manufacture, as well as decomposition products of Sodium isobutyl xanthate. Therefore, the health effects of Isobutyl Alcohol need to be considered in the assessment of sodium isobutyl xanthate. In addition, xanthates decompose on aging to form a number of byproducts, depending on the pH, temperature, etc. Risks associated with xanthate are, therefore, a function of the breakdown of the product or un-reacted raw materials remaining in the product.
- 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
No mutagenic activity of Isobutyl Alcohol detected. 2-methylpropan-1-ol /Isobutyl alcohol/ is both reagents used in the manufacture of sodium O-isobutyl dithiocarbonate . Therefore, 2-methylpropan-1-ol /Isobutyl alcohol/ need to be considered in the assessment of sodium O-isobutyl dithiocarbonate - Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- 2-methylpropan-1-ol /Isobutyl alcohol/ is both reagents used in the manufacture of sodium O-isobutyl dithiocarbonate . Therefore, 2-methylpropan-1-ol /Isobutyl alcohol/ need to be considered in the assessment of sodium O-isobutyl dithiocarbonate
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Principles of method if other than guideline:
- The test substance was tested for mutagenicity in Salmonella typhimurium, using a preincubation protocol. The test was performed in the absence of exogenous metabolic activation, and in the presence of liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters.
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium, other: TA 1535, TA 1537, TA 98, TA97 and TA 100
- Metabolic activation:
- with and without
- Metabolic activation system:
- S-9 mix
- Test concentrations with justification for top dose:
- 100 - 10000 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: [DMSO]
- Justification for choice of solvent/vehicle: none given - Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: Without S9: sodium azide (TA1535 and TA100), 9-aminoacridine (TA97 and TA1537), 4-nitro-o-phenylenediamine (TA98). With S9: 2-aminoanthracene (all strains)
- Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation
DURATION
- Preincubation period: 20 min at 37 °C
- Exposure duration: 2 days at 37 °C
DETERMINATION OF CYTOTOXICITY
- Method: relative total growth- Evaluation criteria:
- Evaluations were made at both the individual trial and overall chemical levels. Individual trials were judged mutagenic: (+), weakly mutagenic (+W), questionable (?), or nonmutagenic (-), depending on the magnitude of the increase of his+ revertants, and the shape of the dose-response. A trial was considered questionable (?) if the dose-response was judged insufficiently high to support a call of "+ W", if only a single dose was elevated over the control, or if the increase seen was not dose related. The distinctions between a questionable mutagenic response and a nonmutagenic or weak mutagenic response and between a weak mutagenic response and mutagenic response are highly subjective. It was not necessary for a response to reach twofold over background for a chemical to be judged mutagenic.
A chemical was judged mutagenic (+) or weakly mutagenic (+W) if it produced a reproducible dose-related response over the solvent control in replicate trials. A chemical was judged questionable (?) if the results of individual trials were not reproducible, if increases in his+ revertants did not meet the criteria for a "+W" response, or if only single doses produced increases in his' revertants in repeat trials.
Chemicals were judged nonmutagenic (-) if they did not meet the criteria for a mutagenic or questionable response. The chemicals were decoded by the chemical repository only after a determination had been made regarding their mutagenicity or nonmutagenicity. - Statistics:
- no data
- Species / strain:
- S. typhimurium, other: TA 1535, TA 1537, TA97, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- reduction of the background lawn at the highest concentration tested in some strains without S-9 mix
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- reduction of the background lawn at the highest concentration tested in some strains without S-9 mix
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- reduction of the background lawn at the highest concentration tested in some strains without S-9 mix
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 97
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- reduction of the background lawn at the highest concentration tested in some strains without S-9 mix
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- reduction of the background lawn at the highest concentration tested in some strains without S-9 mix
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- reduction of the background lawn at the highest concentration tested in some strains without S-9 mix
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- reduction of the background lawn at the highest concentration tested in some strains without S-9 mix
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- ADDITIONAL INFORMATION ON CYTOTOXICITY:
Reduction of the background lawn at the highest concentration tested in TA100, TA1535, TA97 and TA98 without S-9 mix
Alcohol is both reagents used in the manufacture, as well as decomposition products of Sodium isobutyl xanthate. Therefore, the health effects of Isobutyl Alcohol need to be considered in the assessment of sodium isobutyl xanthate. In addition, xanthates decompose on aging to form a number of byproducts, depending on the pH, temperature, etc. Risks associated with xanthate are, therefore, a function of the breakdown of the product or un-reacted raw materials remaining in the product. - 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
No mutagenic activity of Isobutyl Alcohol detected. 2-methylpropan-1-ol /Isobutyl alcohol/ is both reagents used in the manufacture of sodium O-isobutyl dithiocarbonate . Therefore, 2-methylpropan-1-ol /Isobutyl alcohol/ need to be considered in the assessment of sodium O-isobutyl dithiocarbonate . - Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- 2-methylpropan-1-ol /Isobutyl alcohol/ is both reagents used in the manufacture of sodium O-isobutyl dithiocarbonate . Therefore, 2-methylpropan-1-ol /Isobutyl alcohol/ need to be considered in the assessment of sodium O-isobutyl dithiocarbonate
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Principles of method if other than guideline:
- The test substance was evaluated for mutagenic effects by the hypoxanthine-guanine-phosphoribosyl transferase gene mutation test (HPRT test).
- GLP compliance:
- not specified
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- hypoxanthine-guanine-phosphoribosyl transferase gene
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- Type and identity of media: MEM Eagle medium (V79 cells) supplemented with 10% heat-inactivated fetal calf serum (FCS), 2 mM L-glutamine,
100 IU/ml penicillin and streptomycin.
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: no data
- Periodically checked for karyotype stability: no data
- Periodically "cleansed" against high spontaneous background: no data- Metabolic activation:
- with and without
- Metabolic activation system:
- S-9 mix
- Test concentrations with justification for top dose:
- up to 107 mM
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: [no data]
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 2 hours
- Expression time (cells in growth medium): 7 days
- Selection time (if incubation with a selection agent): 7 days
- Fixation time (start of exposure up to fixation or harvest of cells): ca. 14 days
SELECTION AGENT (mutation assays): 6-thioguanine
DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency - Evaluation criteria:
- The test compound was classified as a mutagen when it was able to enhance in a concentration-depended manner the spontaneous HPRT frequency by a factor of three or more.
- Statistics:
- no data
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Remarks:
- no cytotoxicity observed up to 107 mM
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- No mutagenic activity of Isobutyl Alcohol detected.2-methylpropan-1-ol /Isobutyl alcohol/ is both reagents used in the manufacture of sodium O-isobutyl dithiocarbonate . Therefore, 2-methylpropan-1-ol /Isobutyl alcohol/ need to be considered in the assessment of sodium O-isobutyl dithiocarbonate
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results:negative
No mutagenic activity of Isobutyl Alcohol detected.2-methylpropan-1-ol /Isobutyl alcohol/ is both reagents used in the manufacture of sodium O-isobutyl dithiocarbonate . Therefore, 2-methylpropan-1-ol /Isobutyl alcohol/ need to be considered in the assessment of sodium O-isobutyl dithiocarbonate . - Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- 2-methylpropan-1-ol /Isobutyl alcohol/ is both reagents used in the manufacture of sodium O-isobutyl dithiocarbonate . Therefore, 2-methylpropan-1-ol /Isobutyl alcohol/ need to be considered in the assessment of sodium O-isobutyl dithiocarbonate.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Principles of method if other than guideline:
- The test substance was evaluated for mutagenic effects in the L5178Y thymidine kinase mouse lymphoma cell assay.
- GLP compliance:
- not specified
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- thymidine kinase gene
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- - Type and identity of media: The cells were maintained in Fischer's medium for leukemic cells of mice with 10% horse serum and sodium pyruvate.
Cloning medium consisted of Fischer's medium with 10 % horse serum, sodium pyruvate, and 0 .35% Noble agar. Selection medium was made from cloning medium by the addtion of 5 ml BrdU to 100 ml cloning medium.
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: no data
- Periodically checked for karyotype stability: no data
- Periodically "cleansed" against high spontaneous background: yes - Metabolic activation:
- with and without
- Metabolic activation system:
- S-9 mix
- Test concentrations with justification for top dose:
- up to 12.5 µl/ml without activation (10 mg/ml); up to 6.25 µg/ml (5 mg/ml) with activation
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: [water]
- Justification for choice of solvent/vehicle: Isobutyl Alcohol, was partially soluble in sterile, deionized water at a concentration of 250 µl/ml and was then further diluted for testing. - Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- without S-9 mix
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- no
- Positive control substance:
- other: Dimethylnitrosamine
- Remarks:
- with S-9 mix
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 4 hours at 37 °C
- Expression time (cells in growth medium): 2-3 days
- Selection time (if incubation with a selection agent): 10 days
- Fixation time (start of exposure up to fixation or harvest of cells): ca. 12-13 days
SELECTION AGENT (mutation assays): bromodeoxyuridine (BrdU)
DETERMINATION OF CYTOTOXICITY
- Method: relative total growth - Evaluation criteria:
- A compound is considered mutagenic in this assay if:
- A dose-response relationship is observed over 3 of the 5 dose levels employed.
- The minimum increase at the low level of the dose-response curve is at least 2.5 times greater than the solvent and/or negative control values.
- The solvent and negative control data are within the normal range of the spontaneous background for the TK locus.
Occasionally, a single point within a concentration range will show an increase 2.5 times greater than the spontaneous background. If the increase is at the high dose, is reproducible, and if an additional higher dose level is not feasible because of toxicity, the chemical can be considered mutagenic, if the increase is internal within the dose range and is not reproducible, the increase will normally be considered aberrant. If the internal increase is reproducible, several doses clustered around the positive concentration will be examined to either confirm or reject the reliability of the effect. - Statistics:
- no data
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- highly cytotoxic (survival at 3%) at 12.5 µl/ml without S-9 mix
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- ADDITIONAL INFORMATION ON CYTOTOXICITY:
The test substance was highly cytotoxic at 12.5 µl/ml when tested without S-9 mix. At all other concentration tested with and without S-9 mix, the relative growth was > 30%.
Isobutyl Alcohol is both reagents used in the manufacture, as well as decomposition products of Sodium isobutyl xanthate. Therefore, the health effects of Isobutyl Alcohol need to be considered in the assessment of sodium isobutyl xanthate. In addition, xanthates decompose on aging to form a number of byproducts, depending on the pH, temperature, etc. Risks associated with xanthate are, therefore, a function of the breakdown of the product or un-reacted raw materials remaining in the product. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results: negative
No mutagenic activity of Isobutyl Alcohol detected.2-methylpropan-1-ol /Isobutyl alcohol/ is both reagents used in the manufacture of sodium O-isobutyl dithiocarbonate. Therefore, 2-methylpropan-1-ol /Isobutyl alcohol/ need to be considered in the assessment of sodium O-isobutyl dithiocarbonate. - Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- other: published data
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Dithiocarbamates are related compounds to xanthates. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium hydroxide: They arise from the reaction of the amine with CS2
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- yes
- Remarks:
- At least duplicate cultures must be used for each experimental point. Only one harvest time was used.
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 84-2
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- other: Chinese hamster overy cells
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix
- Test concentrations with justification for top dose:
- 3.1, 12.5, 25 ng/ml (without S-9 mix)
125, 500, 1000 ng/ml (with S-9 mix) - Vehicle / solvent:
- DMSO
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: Mitomycin C, Cyclophosphamide
- Species / strain:
- other: Chinese hamster overy cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results :negative
No mutagenic activity of Ziram detected. Dithiocarbamates are related compounds to xanthates. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium hydroxide: They arise from the reaction of the amine with CS2
Referenceopen allclose all
Dose level [ng/mL] |
No. of aberrant cells [%] |
Dose level [ng/mL] |
No. of aberrant cells [%] |
||
With MA |
Without MA |
||||
Exc. gaps |
Inc. gaps |
Exc. gaps |
Inc. gaps |
||
125 |
4.5 |
4.5 |
3.1 |
2.0 |
2.0 |
500 |
3.5 |
4.5 |
12.5 |
2.5 |
2.5 |
1000 |
3.5 |
3.5 |
25.0 |
4.0 |
4.0 |
Solvent |
4.25 |
4.75 |
Solvent |
2.25 |
2.25 |
Positive control |
38.5 |
38.5 |
Positive control |
29.0 |
29.0 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- 2-methylpropan-1-ol /Isobutyl alcohol/ is both reagents used in the manufacture of sodium O-isobutyl dithiocarbonate . Therefore, 2-methylpropan-1-ol /Isobutyl alcohol/ need to be considered in the assessment of sodium O-isobutyl dithiocarbonate
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Germany
- Age at study initiation: 5-8 weeks
- Weight at study initiation: mean: 26 g
- Assigned to test groups randomly: [yes, under following basis: Male and female animals were assigned to the test groups according to a randomization plan prepared with an appropriate computer program.]
- Housing: in groups of 5 during the acclimation period, individually later on
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 3-5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: [olive oil]
- Justification for choice of solvent/vehicle: Due to the insolubility of the test substance in water, olive oil was selected as the vehicle, which had been demonstrated to be suitable in the in vivo micronucleus test and for which historical data are available.
- Concentration of test material in vehicle: 5 g/100 ml; 10 g/100 ml and 20 g/100 ml
- Amount of vehicle (if gavage or dermal): 10 ml/kg - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
The substance to be administered per kg body weight was dissolved in olive oil and prepared immediately before administration.
- The 500 mg/kg group was given 500 mg test substance/kg body weight or 10 ml/kg body weight of a solution with a concentration of 5 g/100 ml.
- The 1000 mg/kg group was given 1000 mg test substance/kg body weight or 10 ml/kg body weight of a solution with a concentration of 10 g/100 ml.
- The 2000 mg/kg groups were given 2000 mg test substance/kg body weight or 10 ml/kg body weight of a solution with a concentration of 20 g/100 ml. - Duration of treatment / exposure:
- single application
- Frequency of treatment:
- single application
- Post exposure period:
- 24 and 48 hours
- Remarks:
- Doses / Concentrations:
500, 1000, 2000 mg/kg bw
Basis:
nominal conc. - No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide (CPP); vincristine sulphate (VCR)
- Justification for choice of positive control(s): Both positive control articles (CPP and VPR) are well-defined clastogens and aneugens respectively.
- Route of administration: orally or intraperitoneally
- Doses / concentrations: 20 mg/kg bw (CPP) / 0.15 mg/kg bw (VCR) - Tissues and cell types examined:
- In general, 2000 polychromatic erythrocytes (PCE) from each of the male and female animals of every test group are evaluated and investigated for micronuclei (MN) . The normochromatic erythrocytes (NCE) which occur are also scored. The cells were prepared from the bone marrow of two femora from animals either sacrificed 24 or 48 hours after dosing.
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
In a pretest for the determination of the acute oral toxicity, all animals (male and female) survived treatment with 2000 mg/kg body weight recommended as the highest dose according to the OECD Guideline. As clinical signs only piloerection was observed.
Therefore, a dose of 2000 mg/kg body weight was selected as the highest dose in the present cytogenetic study. 1000 mg/kg and 500 mg/kg body weight were administered as further doses.
TREATMENT AND SAMPLING TIMES (in addition to information in specific fields):
The animals were treated once and samples of bone marrow were taken 24 hours and 48 hours after the treatment.
DETAILS OF SLIDE PREPARATION:
The bone marrow was prepared according to the method described by SCHMID, W.
- The two femora were prepared by dissection and removing all soft tissues.
-After cutting off the epiphyses, the bone marrow was flushed out of the diaphysis into a centrifuge tube using a cannula filled with fetal calf serum which was at 37°C (about 2 ml/femur).
-The suspension was mixed thoroughly with a pipette, centrifuged at 300 x g for 5 minutes, the supernatant was removed and the precipitate was resuspended in about 50 µl fresh FCS.
- 1 drop of this suspension was dropped onto clean microscopic slides, using a Pasteur pipette. Smears were prepared using slides with ground edges, the preparations were dried in the air and subsequently stained. The slides were stained in eosin and methylene blue solution for 5 minutes (May Grünwald solution modified = Wrights solution), rinsed in purified water and then placed in fresh purified water for 2 or 3 minutes. They were finally stained in 7.5% Giemsa solution for 15 minutes. After being rinsed twice in purified water and clarified in xylene, the preparations were mounted using Corbit-Balsam
METHOD OF ANALYSIS:
In general, 2000 polychromatic erythrocytes (PCE) from each of the male and female animals of every test group are evaluated and investigated for micronuclei (MN). The normochromatic erythrocytes (NCE) which occur are also scored. The following parameters are recorded:
- Number of polychromatic erythrocytes
- Number of polychromatic erythrocytes containing micronuclei
The increase in the number of micronuclei in polychromatic erythrocytes of treated animals as compared with the solvent control group provides an index of a chromosome-breaking (clastogenic) effect or of a spindle activity of the substance tested.
- Number of normochromatic erythrocytes
- Number of normochromatic erythrocytes containing micronuclei
The number of micronuclei in normochromatic erythrocytes at the early sacrifice intervals shows the situation before test substance administration and may serve as a control value. A substance-induced increase in the number of micronuclei in normocytes may be found with an increase in the duration of the sacrifice intervals.
- Ratio of polychromatic to normochromatic erythrocytes
An alteration of this ratio indicates that the test substance actually reached the target
Individual animals with pathological bone marrow depression may be identified and excluded from the evaluation.
- Number of small micronuclei (d < D/4) and of large micronuclei (d > D/4) (d = diameter of micronucleus, D = cell diameter)
The size of micronuclei may give an indication on the possible mode of action of the test substance, i.e. a clastogenic or a spindle poison effect.
Slides were coded before microscopic analysis. - Evaluation criteria:
- The test chemical is to be considered positive in this assay if the following criteria are met:
- A dose-related and significant increase in the number of micronucleated polychromatic erythrocytes at any of the intervals.
- The proportion of cells containing micronuclei exceeded both the values of the concurrent negative control range and the negative historical control range.
A test substance is generally considered negative in this test system if:
- There was no significant increase in the number of micronucleated polychromatic erythrocytes at any dose above concurrent control frequencies and at any time.
- The frequencies of cells containing micronuclei were within the historical control range. - Statistics:
- The statistical evaluation of the data was carried out using the program system MUKERN (BASF Aktiengesellschaft).
The number of micronuclei in polychromatic erythrocytes was analyzed.
A comparison of the dose group with the vehicle control was carried out using the Wilcoxon test for the hypothesis of equal medians. Here, the relative frequencies of cells with micronuclei of each animal were used . If the results of this test were significant, labels (* for p < 0.05, ** for p < 0 .01) wereprinted with the group means in the tables. This test was performed one-sided. - Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- narcotic like state and piloerection
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: 2000 mg/kg
- Clinical signs of toxicity in test animals: piloerection
RESULTS OF DEFINITIVE STUDY
The single oral administration of olive oil in a volume of 10 ml/kg body weight led to 1.5 ‰ polychromatic erythrocytes containing micronuclei after the 24-hour sacrifice interval or to 1.1 ‰ after the 48-hour sacrifice interval.
After the single administration of the highest dose of 2000 mg/kg body weight, 1.8 ‰ polychromatic erythrocytes containing micronuclei were found after 24 hours and 1.3‰ after 48 hours.
In the two lower dose groups, rates of micronuclei of about 1.6 ‰ (1000 mg/kg group) and 1.5 ‰ (500 mg/kg group) were detected after a sacrifice interval of 24 hours in each case.
With 17.9‰ the positive control substance cyclophosphamide for clastogenicity, led to the expected increase in the number of polychromatic erythrocytes containing exclusively small micronuclei at a dose level of 20 mg/kg body weight.
With 67.3 ‰ the positive control vincristine for spindle poison effects also led to a clearly enhanced number of polychromatic erythrocytes containing micronuclei with the expected amount of large micronuclei, i.e. 8.0 ‰.
The number of normochromatic erythrocytes containing micronuclei did not differ to any appreciable extent in the negative control or in the various dose groups at any of the sacrifice intervals.
Thus, the test substance Isobutanol did not lead to any increase in the rate of micronuclei. The number of normochromatic or polychromatic erythrocytes containing small micronuclei (d < D/4) or large micronuclei (d > D/4) did not deviate from the vehicle control value at any of the sacrifice intervals and was within the historical control range.
No inhibition of erythropoiesis induced by the treatment of mice with Isobutanol was detected the ratio of polychromatic to normochromatic erythrocytes was always in the same range as that of the control values in all dose groups. - Conclusions:
- Interpretation of results: negative
Oral gavage dose of 500, 1,000 or 2,000 mg/kg of isobutanol did not have any chromosome-damaging (clastogenic) effect, and there were no
indications of any impairment of chromosome distribution in the course of mitosis.
2-methylpropan-1-ol /Isobutyl alcohol/ is both reagents used in the manufacture of sodium O-isobutyl dithiocarbonate . Therefore, 2-methylpropan-1-ol /Isobutyl alcohol/ need to be considered in the assessment of sodium O-isobutyl dithiocarbonate - Endpoint:
- in vivo mammalian germ cell study: cytogenicity / chromosome aberration
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- other: published data
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Dithiocarbamates are related compounds to xanthates. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium hydroxide: They arise from the reaction of the amine with CS2
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 483 (Mammalian Spermatogonial Chromosome Aberration Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.23 (Mammalian Spermatogonial Chromosome Aberration Test)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 84-2
- GLP compliance:
- yes
- Type of assay:
- mammalian germ cell cytogenetic assay
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- - Source: Charles River, Germany
- Age at study initiation: min. 10 weeks
- Weight at study initiation: ca. 30 g - Route of administration:
- oral: gavage
- Vehicle:
- 0.5% carboxymethylcellulose
- Duration of treatment / exposure:
- 6, 24 and 48 h
- Frequency of treatment:
- Single application
- Post exposure period:
- n.a.
- Remarks:
- Doses / Concentrations:
20, 67 and 200 mg/kg b.w.
Basis:
nominal conc. - No. of animals per sex per dose:
- 5 males (positive control only 4)
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide (CPA)
- Dose: 140 mg/kg b.w. - Tissues and cell types examined:
- Spermatogonia
- Details of tissue and slide preparation:
- In the test article and the negative control groups 100 well spread metaphases per animal were scored for cytogenetic damage on coded slides. In the positive control group 50 metaphases per animal were scored. Only metaphases with the characteristic chromosome number of 40 were included in the analysis. To describe a cytotoxic effect the mitotic index (% cells in mitosis) was determined.
Five animals per test group were evaluated as described. The remaining animals of each test group were evaluated in case animals died in its test group. - Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- Tested in pre-experiments.
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Conclusions:
- Interpretation of results: negative
No mutagenic activity of Ziram detected. Dithiocarbamates are related compounds to xanthates. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium hydroxide: They arise from the reaction of the amine with CS2 - Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- other: published data
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Dithiocarbamates are related compounds to xanthates. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium hydroxide: They arise from the reaction of the amine with CS2
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.11 (Mutagenicity - In Vivo Mammalian Bone-Marrow Chromosome Aberration Test)
- GLP compliance:
- yes
- Type of assay:
- chromosome aberration assay
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Source: BRL Tierfarm Füllinsdorf, Switzerland
- Age at study initiation: min. 10 weeks
- Weight at study initiation: ca. 30 g - Route of administration:
- oral: gavage
- Vehicle:
- Carboxymethylcellulose
- Duration of treatment / exposure:
- 6, 24 and 48 h
- Frequency of treatment:
- Single application
- Post exposure period:
- n.a.
- Remarks:
- Doses / Concentrations:
0, 40, 120 and 400 mg/kg b.w.
Basis:
nominal conc. - No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide (CPA)
- Dose: 20 mg/kg b.w. - Tissues and cell types examined:
- Bone marrow cells
- Details of tissue and slide preparation:
- At least 50 well spread metaphases per animal were scored for cytogenetic damage on coded slides. Only metaphases with the characteristic chromosome number of 40 were included in the analysis. To describe a cytotoxic effect the mitotic index (% cells in mitosis; 1000 cells are scored) was determined.
Five animals per sex and group were evaluated as described. The remaining animal of each test group was evaluated in case an animal died in its test group spontaneously or due to gavage error. - Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- Tested in pre-experiments.
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Conclusions:
- Interpretation of results: negative
No mutagenic activity of Ziram detected. Dithiocarbamates are related compounds to xanthates. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium hydroxide: They arise from the reaction of the amine with CS2 - Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- other: published data
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Dithiocarbamates are related compounds to xanthates. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium hydroxide: They arise from the reaction of the amine with CS2
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- yes
- Remarks:
- No positive control.
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 84-2
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- CD-1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Source: Charles River, USA
- Age at study initiation: 5-6 weeks
- Weight at study initiation: no data - Route of administration:
- oral: feed
- Duration of treatment / exposure:
- 89 days
- Frequency of treatment:
- daily
- Post exposure period:
- none
- Remarks:
- Doses / Concentrations:
0, 25, 75, 225 and 675 ppm
Basis:
nominal in diet - No. of animals per sex per dose:
- 50
- Control animals:
- yes, plain diet
- Tissues and cell types examined:
- Peripheral blood
- Details of tissue and slide preparation:
- Peripheral blood smears were prepared from 5 male and 5 female animals in each group. The smears were stained using Giemsa then examined by light microscopy for the presence of micronuclei in normochromatic and polychromatic erythrocytes (1000 cells of each type were examined from each animal). The ratio of polychromatic to normochromatic erythrocytes was assessed by examination of at least 1000 erythrocytes from each animal.
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- not examined
- Conclusions:
- Interpretation of results: negative
No mutagenic activity of Ziram detected. Dithiocarbamates are related compounds to xanthates. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium hydroxide: They arise from the reaction of the amine with CS2 - Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- other: published data
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. SIBX readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of SIBX.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- not specified
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- CD-1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories (UK)
- Age at study initiation: 4-5 weeks
- Weight at study initiation: 16.1-26 g
- Assigned to test groups randomly: yes
- Housing: high density polypropylene cages with stainless steel taps
- Diet: ad libitum
- Water: supplied via a polythene bottle and sipper tube
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±2
- Humidity (%): 55 ±15 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light):12 - Route of administration:
- inhalation: vapour
- Vehicle:
- no vehicle used
- Details on exposure:
- TYPE OF INHALATION EXPOSURE: snout only
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
-Animals were exposed to the test material by snout-only inhalation. Prior to exposure of animals, the test material atmospheres were generated for each exposure chamber and samples analysed. Each mouse was placed in an individual polymethyl methacrylate restraining tube so that only the snout protruded. Each restraining tube was marked with the animal and group numbers. The restraining tubes were attached to the appropriate chamber so that the snout of each mouse projected into the lumen of the chamber. When the pre-exposure observations were complete, the syringe pump was switched on and the exposure timed for six hours following a 4.5 minute equilibration period, the theoretical time required for the concentration of vapour to reach 90% of its final value under the conditions of exposure employed (Silver and Arsenal, 1946). After six hours, the test atmosphere
supply was switched off and the mice removed from the restraining tubes for examination. - Duration of treatment / exposure:
- 6 h
- Frequency of treatment:
- once
- Remarks:
- Doses / Concentrations:
0, 467, 1558, 4675 mg/m3 (150, 500, 1500 ppm)
Basis:
nominal conc. - No. of animals per sex per dose:
- 10 (5 for positive control)
- Control animals:
- yes
- Positive control(s):
- chlorambucil
- Route of administration: oral
- Doses / concentrations: 30 mg/kg - Tissues and cell types examined:
- bone marrow erythrocytes
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: based on the preliminary toxicity testing
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): samples were taken 24 and 48 h after treatment
DETAILS OF SLIDE PREPARATION: Animals were killed by cervical dislocation following carbon dioxide inhalation. Femurs from each animal were rapidly dissected out and cleaned of adherent tissue. The epiphyses were cut off to obtain access to the marrow canal. Marrow cells were flushed out with 2.5 ml foetal calf serum using a syringe and needle. The recovered cells were centrifuged at 1000 rpm for five minutes. The bulk of the supernatant fluid was discarded and the cell pellet resuspended in the remaining fluid. Single drops of the cell suspension were transferred to clean, dry slides, two or three smears (for the preliminary toxicity test or main micronucleus test respectively) prepared, and the slides left to air-dry. Following fixation in methanol for ten minutes, they were stained manually in 5% Giemsa stain (in Sorensen's buffer: pH 6.8), washed in buffer, air-dried, cleared for five minutes in xylene and made permanent using DPX mountant.
METHOD OF ANALYSIS: The slides were examined under the light microscope. At high magnification (x 1000, oil immersion) a total of at least 2000 erythrocytes per animal were examined. Each erythrocyte scored was classed as polychromatic or mature. Each erythrocyte scored was also examined for the presence or absence of micronuclei. Thereafter, the frequencies of micronucleated cells per 1000 erythrocytes were calculated. The ratio of polychromatic to mature cells was also determined (indicating the rythm of cell division). The frequency of micronuclei in polychromatic cells provides an index of induced genetic damage. - Evaluation criteria:
- Positive for clastogenicity was a statistically and biologically significant increase in micronucleated polychromatic cells, compared to vehicle control, in at least one treatment group; particularly if supported by evidence of a dose-related response.
- Statistics:
- Mann-Whitney U procedure (Mann and Whitney, 1942), two-tailed test, one-tailed test.
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- not examined
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: 45, 150, 450, 1500, 2000 ppm
- Clinical signs of toxicity in test animals: unconscious and death at 2000 ppm, unconscious, slow and laboured respiration, all extremities red coloured. No adverse reactions to treatment were observed in animals exposed to 450, 150, 45 ppm test substance.
- Evidence of cytotoxicity in tissue analyzed: no bone marrow toxicity observed
- Harvest times: 48 hours
RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): see table
- Ratio of PCE/NCE (for Micronucleus assay): see table - Conclusions:
- Interpretation of results: negative
No evidence of induced chromosomal or other damage leading to the formation of micronuclei in erythrocytes of the bone marrow was detected after exposure of the animals to CS2 via inhalation.
Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. SIBX readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of SIBX.
In addition, xanthates decompose on aging to form a number of byproducts, depending on the pH, temperature, etc. Risks associated with xanthate are, therefore, a function of the breakdown of the product or un-reacted raw materials remaining in the product. - Executive summary:
The effect of carbon disulphide on chromosome structure in the bone marrow erythrocytes of mice was examined. The animals (males and females) were exposed via inhalation snout-only, for 6 h to the following concentrations: 0, 467, 1558, 4675 mg/m3 (0, 150, 500, 1500 ppm). The exposure concentrations were based on a preliminary toxicity test. Chlorambucil (30 mg/kg bw) was used as a positive control, adminstered via the oral route. Animals were sacrifised and examined 24 and 48 h after exposure. No evidence of induced chromosomal or other damage leading to the formation of micronuclei in erythrocytes of the bone marrow was detected, uder the present test condition, after exposure of the animals to CS2 via inhalation. Mice exposed at 1500 ppm, however, showed a small increase in the ratio of polychromatic/mature cells, which may indicate disturbance of erythropoiesis. Carbon disulphide was tested for induction of micronuclei in the bone marrow ertythrocytes of mice according to the OECD Guidelines 474 (1983).
- Endpoint:
- genetic toxicity in vivo, other
- Remarks:
- Type of genotoxicity: other: review paper covering many studies
- Type of information:
- other: published data
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. SIBX readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of SIBX. In addition, xanthates decompose on aging to form a number of byproducts, depending on the pH, temperature, etc. Risks associated with xanthate are, therefore, a function of the breakdown of the product or un-reacted raw materials remaining in the product.
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Review of a large series of publications on studies in which a wide array of methods was applied.
- GLP compliance:
- not specified
- Type of assay:
- other: review paper covering many studies
- Species:
- other: A series of studies with various animal species was reviewed.
- Strain:
- other: A series of studies with various animal species was reviewed.
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Not applicable: review paper.
- Route of administration:
- other: Invasive (injection) and non-invasive (inhalation, oral, dermal) routes were employed in the different studies reviewed.
- Vehicle:
- Not applicable: review paper.
- Details on exposure:
- Not applicable: review paper.
- Duration of treatment / exposure:
- Not applicable: review paper.
- Frequency of treatment:
- Not applicable: review paper.
- Conclusions:
- Interpretation of results: negative
In the majority of the in vivo tests assessing CS2 mutagenic potential, a negative result was obtained, except for one case. The validity of the studies is uncertain due to technical issues (e.g. invalid controls).
Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. SIBX readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of SIBX.
In addition, xanthates decompose on aging to form a number of byproducts, depending on the pH, temperature, etc. Risks associated with xanthate are, therefore, a function of the breakdown of the product or un-reacted raw materials remaining in the product. - Executive summary:
In male and female rats inhaling 63 or 125 mg carbon disulfide/m3, 7 hours per day for 1 or 5 days, there was no significant increase in the frequency of chromosomal aberrations in bone marrow cells (Belisles et al., 1980). In another study (Vasil’eva, 1982), oral exposure to carbon disulfide gave a mutagenic response, manifested as chromosomal aberrations and polyploid cells in the bone marrow of female rats and in rat embryos exposed on days 10–13 of gestation. According to the reviewer,'it is difficult to assess the validity of these findings, as the reporting was brief e.g., the statistical significance was often not indicated and the effective dose was not reported, except to indicate that it was one-tenth of the LD50 '. In the investigation of Belisles et al. (1980), male rats were exposed to 63–125 mg/m3 of CS2, 7 h/d for 5 d; no significant increase in dominant lethal mutations was observed, nor was there a dose related increase in sperm abnormalities in rats or mice exposed according to the same protocol. However, lack of an effect on sperm abnormalities in positive control rats suggests that there was a problem with the test methods in this study.
Referenceopen allclose all
Group |
Dose [mg/kg] |
Exposure [h] |
No. of cells scored |
Aberrant cells [%] |
Mitotic index [%] |
|
Incl. gaps |
Excl. gaps |
|||||
Ziram |
200 |
6 |
500 |
0.0 |
0.0 |
1.40 |
Vehicle control |
0 |
24 |
500 |
0.4 |
0.2 |
2.80 |
Ziram |
20 |
24 |
500 |
0.0 |
0.0 |
1.40 |
Ziram |
67 |
24 |
500 |
0.2 |
0.0 |
2.34 |
Ziram |
200 |
24 |
500 |
0.2 |
0.2 |
1.84 |
Positive control |
140 |
24 |
200 |
8.0 |
7.5 |
0.34 |
Ziram |
200 |
48 |
500 |
0.8 |
0.4 |
1.16 |
Group |
Dose [mg/kg] |
Exposure [h] |
No. of cells scored |
Aberrant cells [%] |
Mitotic index [%] |
|
Incl. gaps |
Excl. gaps |
|||||
Ziram |
400 |
6 |
500 |
0.4 |
0.2 |
3.54 |
Vehicle control |
0 |
24 |
500 |
0.4 |
0.0 |
4.91 |
Ziram |
40 |
24 |
500 |
1.0 |
0.6 |
4.03 |
Ziram |
120 |
24 |
500 |
0.6 |
0.0 |
5.50 |
Ziram |
400 |
24 |
500 |
1.6 |
1.2 |
3.52 |
Positive control |
20 |
24 |
500 |
28.4 |
27.8 |
5.00 |
Ziram |
400 |
48 |
500 |
0.2 |
0.2 |
5.08 |
Dose level [ppm] |
Ration p/n (mean) |
Incidence mnp (mean) |
Incidence mnn (mean) |
Control |
0.108 |
0.9 |
1.1 |
25* |
0.143 |
0.6 |
1.7 |
75** |
0.124 |
1.2 |
2.0 |
225 |
0.095 |
0.8 |
0.7 |
675 |
0.135 |
0.5 |
1.2 |
p/n Ratio of polychromatic to normochromatic erythrocytes
mnp No. of micronucleated cells observed per 1000 polychromatic erythrocytes
mnn No. of micronucleated cells observed per 1000 normochromatic erythrocytes
* Prepared at 29 ppm initially to allow for loss during storage
** Prepared at 83 ppm initially to allow for loss during storage
The micronucleus test - group means and standard deviations (sd) by sex
test group |
dose (ppm) |
sampling time (h) |
Sex |
total polychromatic cells scored |
total micronucleated polychromatic cells |
mean micronucleated polychromatic cells per 1000 and sd |
total mature cells scored |
total micronucleated mature cells per 1000 and sd |
polychromatic cells/mature cells |
Air |
0 |
24 |
M |
5183 |
7 |
1.3±0.9 |
5652 |
4 |
0.7±0.4 |
F |
5709 |
3 |
0.5±0.5 |
5607 |
3 |
0.6±0.9 |
|||
Carbon disulphide |
150 |
M |
5208 |
2 |
0.4±0.5 |
5871 |
4 |
0.6±0.9 |
|
F |
6030 |
6 |
1.0±0.7 |
5469 |
5 |
0.9±0.8 |
|||
500 |
M |
6194 |
14 |
2.0±1.6 |
5505 |
2 |
0.4±0.5 |
||
F |
5788 |
10 |
1.6±1.1 |
5148 |
3 |
0.6±0.5 |
|||
1500 |
M |
6713 |
8 |
1.0±1.2 |
5089 |
2 |
0.4±0.5 |
||
F |
7640 |
9 |
1.2±0.9 |
5129 |
2 |
0.4±0.5 |
|||
Chlorambucil |
30 mg/kg |
M |
5473 |
322 |
59.0±27.6 |
5176 |
3 |
0.6±0.9 |
|
F |
5807 |
403 |
69.3±27.5 |
5201 |
7 |
1.3±0.8 |
|||
Air |
0 |
48 |
M |
5090 |
4 |
0.8±0.8 |
6101 |
7 |
1.1±0.8 |
F |
5588 |
4 |
0.7±0.8 |
4561 |
1 |
0.2±0.4 |
|||
Carbon disulphide |
150 |
M |
5353 |
2 |
0.4±0.5 |
5699 |
4 |
0.7±0.6 |
|
F |
5976 |
9 |
1.5±1.1 |
5079 |
0 |
0.0±0.0 |
|||
500 |
M |
6153 |
7 |
1.1±1.2 |
5300 |
3 |
0.6±0.9 |
||
F |
6518 |
6 |
0.9±0.6 |
5105 |
2 |
0.4±0.5 |
|||
1500 |
M |
7324 |
8 |
1.0±0.9 |
5072 |
0 |
0.0±0.0 |
||
F |
6558 |
15 |
2.1±1.4 |
5022 |
0 |
0.0±0.0 |
Additional information
Additional information from genetic toxicity in vitro:
No mutagenic activity of CS2 detected in the reliable study of Akzo Chemicals International BV 1992.Carbon disulphide was examined for its mutagenic activity in four histidine-dependent auxotrophs of Salmonella typhimurium, strains TA98, TA100, TA1535, TA1537.Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. SIBX readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of SIBX.
No mutagenic activity of Isobutyl Alcohol detected in the reliable study of Kreja L, Seidel H-J 2002.. Isobutyl Alcohol was examined for its mutagenic activity inChinese hamster lung fibroblasts (V79) cell line.
2-methylpropan-1-ol /Isobutyl alcohol/ is both reagents used in the manufacture of sodium O-isobutyl dithiocarbonate . Therefore, 2-methylpropan-1-ol /Isobutyl alcohol/ need to be considered in the assessment of sodium O-isobutyl dithiocarbonate
No mutagenic activity of Isobutyl Alcohol detectedin the reliable study ofShimizu H, et al.1985. Isobutyl Alcohol was examined for its mutagenic activity in Salmonella typhimurium, strains TA98, TA100, TA1535, TA1537, and TA1538 and E. coli WP2 uvr A.
2-methylpropan-1-ol /Isobutyl alcohol/ is both reagents used in the manufacture of sodium O-isobutyl dithiocarbonate . Therefore, 2-methylpropan-1-ol /Isobutyl alcohol/ need to be considered in the assessment of sodium O-isobutyl dithiocarbonate
In the reliable study of Engelhardt, D. et al.2000, oral gavage dose of 500, 1,000 or 2,000 mg/kg of isobutanol in mouse did not have any chromosome-damaging (clastogenic) effect, and there were noindications of any impairment of chromosome distribution in the course of mitosis.
2-methylpropan-1-ol /Isobutyl alcohol/ is both reagents used in the manufacture of sodium O-isobutyl dithiocarbonate . Therefore, 2-methylpropan-1-ol /Isobutyl alcohol/ need to be considered in the assessment of sodium O-isobutyl dithiocarbonate
No evidence of induced chromosomal or other damage leading to the formation of micronuclei in erythrocytes of the bone marrow was detected after exposure of the mouse to CS2 via inhalationin the reliable study of Akzo Chemicals International BV 1992..
Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. SIBX readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of SIBX.
Justification for selection of genetic toxicity endpoint
Negative in all test conducted.
Justification for classification or non-classification
Based on the hazard assessment of SIBX in section 2.1 and 2.2. in IUCLID 6 available data for the substance and following the “Guidance on Information Requirement and Chemical Safety Assessment R.8. Characterisation of dose [concentration]- response for human health” andaccording to the criteria described in Directive 67/548 and in the CLP Regulation:
Directive 67/548 |
Mutagenicity-Genetic Toxicity Muta. Cat. 1; R46 May cause heritable genetic damage. Muta. Cat. 2; R46 May cause heritable genetic damage. Muta. Cat. 3; R68 Possible risk of irreversible effects. |
CLP |
Germ cell mutagenicity Muta. 1A Muta. 1B Muta. 2 H340: May cause genetic defects <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>. H341: Suspected of causing genetic defects <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>. |
It is concluded that the substance SIBX does not meet the criteria to be classified for human health hazards for Mutagenicity-Genetic Toxicity
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