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EC number: 220-120-9 | CAS number: 2634-33-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 003
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Version / remarks:
- 1997
- GLP compliance:
- yes
- Type of assay:
- mammalian cell gene mutation assay
Test material
- Reference substance name:
- 1,2-benzisothiazol-3(2H)-one
- EC Number:
- 220-120-9
- EC Name:
- 1,2-benzisothiazol-3(2H)-one
- Cas Number:
- 2634-33-5
- Molecular formula:
- C7H5NOS
- IUPAC Name:
- 1,2-benzisothiazol-3(2H)-one
- Test material form:
- solid
Constituent 1
- Specific details on test material used for the study:
- Purity: 77.4% 1,2-Benzisothiazol-3(2H)-one (BIT)
Batch number Bx.L1001
Method
Species / strain
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 fraction
- Test concentrations with justification for top dose:
- Test 1: 0.1 to 3.2 µg/ml and 0.2 to 6.4 µg/ml without and with metabolic activation, respectively.
Test 2: 0.8 to 6.4 µg/ml and 1.6 to 12.8 µg/ml without and with metabolic activation, respectively.
- Details on test system and experimental conditions:
- IUCLID4 Type: Mouse lymphoma assay
Results and discussion
Test results
- Key result
- Species / strain:
- mouse lymphoma L5178Y 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
Applicant's summary and conclusion
- Conclusions:
- Materials and methods
BIT was assayed for mutation at the hprt locus (6-thioguanine resistance) in mouse lymphoma cells using a fluctuation protocol (guideline compliance with OECD 476 (1997) and EC B.17 (2000)). The study consisted of cytotoxicity range-finding experiments followed by two independent experiments, each conducted in the absence and presence of metabolic activation by an Aroclor 1254 induced rat liver post-mitochondrial fraction (S-9).
The initial cytotoxicity range-finding experiment with and without metabolic activation was performed in the concentration range 46.88 to 1512 µg/mL. Since complete toxicity was observed at all concentrations, a second range-finding experiment was performed with and without metabolic activation in the range 0.3906 to 50 µg/mL. On the basis of the results from this second range-finding experiment, Experiment 1 of the main test was performed in the concentration range 0.1 to 3.2 µg/mL in the absence of metabolic activation and in the concentration range 0.2 to 6.4 µg/mL in the presence of metabolic activation. The concentration range was extended in Experiment 2 of the main test to 0.2 to 6.4 µg/mL in the absence of metabolic activation and to 0.4 to 12.8 µg/mL in the presence of metabolic activation.
Cultures with BIT, 4 Nitroquinoline 1-oxide (NQO, positive control in the absence of metabolic activation) or Benzo(a)pyrene (BP, positive control in the presence of metabolic activation) were maintained in flasks for a period of 7 days during which the HPRT mutation would be expressed.
Mutant frequency was assessed for statistical significance. The experiment was considered valid if the mutant frequencies in the solvent control cultures fell within the normal range (not more than three times the historical mean value) and at least one concentration of each of the positive control chemicals induced a clear increase in mutant frequency (the difference between the mutant frequencies was greater than half the historical mean value).
The test substance was considered to be mutagenic if the assay was valid, the mutant frequency of one or more doses was significantly greater than that of the solvent control, and there was a significant dose relationship as indicated by the linear trend analysis and if these effects were reproducible.
Results and discussion
In Experiment 1, the highest dose selected in the presence of S-9 (6.4 µg/mL) could not be analysed due to excessive contamination observed on the mutant plates and the second highest dose tested (4.8 µg/mL) was considered too toxic for selection to determine viability and 6-thioguanine (6TG) resistance (extreme toxicity in one of the replicate cultures was observed). The highest dose analysed in both the absence and presence of S-9 was therefore 3.2 µg/mL, with relative survival being 61% and 44%, respectively. No dose of ideal toxicity (10-20% relative survival) was achieved in the absence or presence of S-9. This was unexpected, based on the results of the cytotoxicity range-finding experiment. However, adequate, dose-related toxicity was demonstrated in the absence and presence of S-9 in Experiment 2, therefore this was not considered to have affected the integrity of the study in any way.
In Experiment 2, the highest doses analysed were 4.8 µg/mL in the absence of S-9 and 6.4 µg/mL in the presence of S 9, with relative survival being 9% and 10%, respectively.
Negative (solvent) and positive control treatments were included in each mutation experiment in the absence and presence of metabolic activation. Mutant frequencies in negative control cultures fell within normal ranges, and clear increases in mutation were induced by the positive control chemicals 4-Nitroquinoline 1-oxide (without metabolic activation) and Benzo(a)pyrene (with metabolic activation). The study was therefore considered valid.
No statistically significant increases in mutant frequency were observed following treatment with BIT at any dose level analysed, in the absence or presence of metabolic activation in Experiment 1, or in the absence of metabolic activation in Experiment 2.
A small but statistically significant increase in mutant frequency was observed at the highest dose analysed in the presence of metabolic activation in Experiment 2 (6.4 µg/mL), compared to the concurrent solvent controls, and a linear trend was observed. The mutant frequency observed at this dose was, however, similar to the historical mean solvent control mutant frequency. Furthermore, the statistically significant increase in mutant frequency was observed at a highly toxic dose, yielding only 10% relative survival. This increase in mutant frequency was therefore considered of little or no biological significance.
Conclusion
Under the conditions employed in this study, BIT did not show conclusive evidence of mutagenic activity. - Executive summary:
A study was conducted to determine the in vitro genotoxic potential of the substance in mammalian cells according to OECD Guideline 476. The test substance was assayed for mutation at the hprt locus (6-thioguanine resistance) in mouse lymphoma cells. The study consisted of cytotoxicity range-finding experiments followed by two independent experiments, each conducted in the absence and presence of metabolic activation by an Aroclor 1254 induced rat liver post-mitochondrial fraction (S-9). The initial cytotoxicity range-finding experiment with and without metabolic activation was performed in the concentration range 46.88 to 1512 µg/mL. Since complete toxicity was observed at all concentrations, a second range-finding experiment was performed with and without metabolic activation in the range 0.3906 to 50 µg/mL. On the basis of the results from this second range-finding experiment, Experiment 1 of the main test was performed in the concentration range 0.1 to 3.2 µg/mL in the absence of metabolic activation and in the concentration range 0.2 to 6.4 µg/mL in the presence of metabolic activation. The concentration range was extended in Experiment 2 of the main test to 0.2 to 6.4 µg/mL in the absence of metabolic activation and to 0.4 to 12.8 µg/mL in the presence of metabolic activation. 4 Nitroquinoline 1 -oxide (in the absence of metabolic activation) or Benzo(a)pyrene (in the presence of metabolic activation) were used as the positive controls in this study. Mutant frequency was assessed for statistical significance. In experiment 1, the highest dose selected in the presence of S-9 (6.4 µg/mL) could not be analysed due to excessive contamination observed on the mutant plates and the second highest dose tested (4.8 µg/mL) was considered too toxic for selection to determine viability and 6 -thioguanine (6TG) resistance. The highest dose analysed in both the absence and presence of S-9 was therefore 3.2 µg/mL, with relative survival being 61% and 44%, respectively. No dose of ideal toxicity (10-20% relative survival) was achieved in the absence or presence of S-9. However, adequate dose-related toxicity was demonstrated in the absence and presence of S-9 in Experiment 2, therefore this was not considered to have affected the integrity of the study in any way. In experiment 2, the highest doses analysed were 4.8 µg/mL in the absence of S-9 and 6.4 µg/mL in the presence of S 9, with relative survival being 9% and 10%, respectively. Mutant frequencies in negative control cultures fell within normal ranges, and clear increases in mutation were induced by the positive controls. The study was therefore considered valid. No statistically significant increases in mutant frequency were observed following treatment at any of the non-toxic doses analysed. Under the study conditions, the substance was not considered to be mutagenic in mouse lymphoma cells (Lloyd, 2003).
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