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EC number: 500-109-8 | CAS number: 43011-20-7
- 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 cytogenicity / micronucleus study
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- migrated information: read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Study period:
- 2014-2015
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study under GLP
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 015
- Report date:
- 2015
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Guideline No. 487
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- in vitro mammalian cell micronucleus test
Test material
- Reference substance name:
- 5-Isobenzofurancarboxylic acid, 1,3-dihydro-1,3-dioxo-, reaction products with 1,2-propanediol
- IUPAC Name:
- 5-Isobenzofurancarboxylic acid, 1,3-dihydro-1,3-dioxo-, reaction products with 1,2-propanediol
- Reference substance name:
- 5-Isobenzofurancarboxylic acid, 1,3-dihydro-1,3-dioxo-, polymer with 1,2-propanediol
- EC Number:
- 613-407-9
- Cas Number:
- 63948-88-9
- IUPAC Name:
- 5-Isobenzofurancarboxylic acid, 1,3-dihydro-1,3-dioxo-, polymer with 1,2-propanediol
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- Name:ZAN 573.
Synonym:ZAN 573/100 Both denominations refer to the same test item.
Batch number:130072591.
Description:
yellow to brown solid (coarse powder).
Container:one tube.
Storage condition:at room temperature.
Date of receipt:26 August 2014.
Re-test date:24 January 2016.
Molecular weight:UVCB-substance composed of constituents with varying molecular weight.
Purity:100%.
Correction factor applied:none
Constituent 1
Constituent 2
Method
- Target gene:
- Micronuclei formation was the chromosome aberration examined
Species / strain
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- liver S9 fraction from rats induced with PB and BNF
- Test concentrations with justification for top dose:
- 2.29, 6.86, 20.6, 61.7, 185.2, 555.6, 1666.7 and 5000 µg/mL.
- Vehicle / solvent:
- according to available solubility data, the vehicle was dimethylsulfoxide (DMSO)
Controls
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- ethylmethanesulphonate
- other: DMBA,
- Details on test system and experimental conditions:
- Cell cultures were grown in 24-well plates at 37°C in a humidified atmosphere of 5% CO2/95% air in culture medium. Each treatment was coupled to an assessment of cytotoxicity. In the preliminary toxicity test for the substance without S9 activation, the exposure was 3 hours, with a 24 hour recovery period, and also a 24 hour exposure with a 20 hour recovery period. The exposure period for the substance with S9 activation was 3 hours, with a 24 hour recovery period. For the main study without S9, the exposure period without S9 activation was of 3 hours duration, with a 24 hour recovery period, followed by a second study of 24 hour exposure duration with a 20 hour recovery period. For the main study of the substance with S9 activation, there were two experiments where the exposure duration was 3 hours, with a 24 hour recovery period.
Cytotoxicity was evaluated by determining the PD (Population Doubling) of cells.
After the final cell counting, the cells were washed twice and fixed. Cells from three dose-levels of the test item treated cultures were dropped onto clean glass slides. The slides were air-dried before being stained in 5% Giemsa. Slides from vehicle and positive controls cultures were also prepared as described above. All slides were coded before a "blinded" analysis. For each main experiment (with or without S9 mix), micronuclei were analyzed for three dose-levels of the test item, for the vehicle and the positive controls, in 1000 mononucleated cells per culture (total of 2000 mononucleated cells per dose).
Number of cells with micronuclei and number of micronuclei per cell were recorded separately for each treated and control culture.
The test item was dissolved in dimethylsulfoxide (DMSO). - Evaluation criteria:
- Evaluation of a positive response: a test item is considered to have clastogenic and/or aneugenic potential, if all the following criteria were met:
1. a dose-related increase in the frequency of micronucleated cells was observed,
2. for at least one dose-level, the frequency of micronucleated cells of each replicate culture was above the corresponding vehicle historical range,
3. a statistically significant difference in comparison to the corresponding vehicle control was obtained at one or more dose-levels.
Evaluation of a negative response: a test item is considered negative if none of the criteria for a positive response were met. - Statistics:
- Chi-square analysis was applied with a significance level of 0.05.
Results and discussion
Test results
- 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:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- RANGE-FINDING/SCREENING STUDIES:
WITHOUT S9 METABOLIC ACTIVATION:
Following the 3-hour treatment without S9 mix, a severe toxicity was observed at dose-levels ≥ 100 µg/mL, as shown by a 100% decrease in the PD.
Following the 24-hour treatment without S9 mix, a slight to severe toxicity was observed at dose-levels ≥ 100 µg/mL, as shown by a 39 to 100% decrease in the PD.
Following the 3-hour treatment with S9 mix, a moderate to severe toxicity was observed from the lowest tested dose-level (i.e. 10 µg/mL), as shown by a 58 to 100% decrease in the PD.
Based on toxicity data obtained from the preliminary experiment, the following dose-levels were tested using a treatment volume of 1% (v/v) in culture medium: 0.78, 1.56, 3.13, 6.25, 12.5, 25, 50 and 100 µg/mL. However, the highest dose-level of 100 µg/mL induced neither the recommended level of cytotoxicity nor a precipitation in the culture medium. No slides were prepared from this experiment. A new treatment was thus performed as the first experiment.
The following range of dose-levels was used in the first experiment (3 h treatment + 24 h recovery) and second experiment (24 h treatment + 20 h recovery): 2.29, 6.86, 20.6, 61.7, 185.2, 555.6, 1666.7 and 5000 µg/mL.
A slight to marked precipitate was observed in the culture medium exclusively at the beginning of the treatment periods at dose levels ≥ 555.6 µg/mL and ≥ 1666.7 µg/mL, in the first and second experiments, respectively.
Following the 3-hour treatment, a slight to severe toxicity was induced at dose-levels ≥ 61.7 µg/mL as shown by a 28 to 100% decrease in the PD.
Following the 24-hour treatment, a moderate to severe toxicity was induced at dose-levels ≥ 555.6 µg/mL as shown by a 50 to 100% decrease in the PD.
Based on the level of cytotoxicity, the dose-levels selected for micronucleus analysis were as follows:
6.86, 20.6 and 61.7 µg/mL for the 3-hour treatment, the latter inducing a 28% decrease in the PD, and the higher dose-level being too cytotoxic,
61.7, 185.2 and 555.6 µg/mL for the 24-hour treatment, the latter inducing the recommended level of toxicity (50% decrease in the PD).
WITH S9 METABOLIC ACTIVATION:
Based on toxicity data obtained from the preliminary experiment, the following dose-levels were tested using a treatment volume of 1% (v/v) in culture medium: 0.78, 1.56, 3.13, 6.25, 12.5, 25, 50 and 100 µg/mL. However, the highest dose-level of 100 µg/mL induced neither the recommended level of cytotoxicity nor a precipitation in the culture medium. No slides were prepared from this experiment. A new treatment was thus performed as first experiment.
With a treatment volume of 1% (v/v) in culture medium, the dose-levels used for treatment were as follows:
2.29, 6.86, 20.6, 61.7, 185.2, 555.6, 1666.7 and 5000 µg/mL for the first experiment,
0.25, 0.76, 2.29, 6.86, 20.6, 61.7, 185.2 and 555.6 µg/mL for the second experiment.
In the first experiment, a slight to severe toxicity was induced at dose-levels ≥ 6.86 µg/mL, as shown by a 25 to 100% decrease in the PD.
In the second experiment, a severe toxicity was induced at dose-levels ≥ 185.2 µg/mL, as shown by a 100% decrease in the PD.
Based on the level of cytotoxicity, the dose-levels selected for micronucleus analysis were as follows:
2.29, 6.86 and 20.6 µg/mL for the first experiment, the latter inducing the recommended level of cytotoxicity (50% decrease in the PD).
6.86, 20.6 and 61.7 µg/mL for the second experiment, higher dose-levels being too cytotoxic. - Remarks on result:
- other: strain/cell type:
- Remarks:
- Migrated from field 'Test system'.
Any other information on results incl. tables
No increase in the frequency of micronucleated cells was observed in any of the 3 three consecutive doses selected for evaluation.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
negative
ZAN 573 did not induce chromosome damage in cultured L5178Y TK+/-mouse lymphoma cells, in the absence or in the presence of metabolic activation. This study is informative for evaluation of the toxicity of members of the cyclic acid anhydride category, and is adequate for filling the data requirement for the registration of this substance. It is valid for hazard classification and risk assessment.
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