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EC number: 204-506-4 | CAS number: 121-91-5
- 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 cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1990-08-14 to 1991-03-15
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 991
- Report date:
- 1991
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- yes
- Remarks:
- : test material purity is not reported
- GLP compliance:
- yes
- Type of assay:
- other: in vitro mammalian chromosome aberration test
Test material
- Reference substance name:
- Isophthalic acid
- EC Number:
- 204-506-4
- EC Name:
- Isophthalic acid
- Cas Number:
- 121-91-5
- Molecular formula:
- C8H6O4
- IUPAC Name:
- isophthalic acid
- Test material form:
- other: white solid
- Details on test material:
- - Name of test material (as cited in study report): Isophthalic acid
- Physical state: White solid
- Lot/batch No.: MIL-62
- Storage condition of test material: Room temperature, protected from light
Constituent 1
- Specific details on test material used for the study:
- Name of test material (as cited in study report): Isophthalic acid
- Physical state: White solid
- Lot/batch No.: MIL-62
- Storage condition of test material: Room temperature, protected from light
Method
- Target gene:
- The observation of chromosome aberrations in Chinese hamster ovary (CHO) cells is an acceptable clastogenic activity.
Species / strain
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Details on mammalian cell type (if applicable):
- - Type and identity of media:
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: no, in order to assure the karyotypic stability of the cell line, cells were not used beyond passage 20
- Periodically "cleansed" against high spontaneous background: not stated - Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- Arocolor-induced S-9
- Test concentrations with justification for top dose:
- Test concentrations 625, 1,250, 2,500 and 5,000 ug/ml were used.
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: No justification was provided.
Controls
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- activated and non-activated
- Positive control substance:
- triethylenemelamine
- cyclophosphamide
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: In medium
DURATION
- Preincubation period:16-24 hours
- Exposure duration: 6 hours exposure
- Expression time (cells in growth medium): 24 hours
- Selection time (if incubation with a selection agent):
- Fixation time (start of exposure up to fixation or harvest of cells):12 hours (due to observations of a slight delay in cell cycle kinetics in the absence of S-9 mix and 10 hours in the absence of any observed delay in cell cycle kinetics in the presence of S-9 mix
NUMBER OF REPLICATIONS: 2
NUMBER OF CELLS EVALUATED: 100 per duplicate
DETERMINATION OF CYTOTOXICITY
- Method: The toxic effects of treatment were based upon mitotic inhibition relative to the solvent-treated control and were presented for the toxicity and aberration study.
OTHER: A minimum of 200 metaphase spreads (100 duplicate flask) were examined and scored for chromatid-type and chromosome-type aberrations. chromatid-type aberations inculded chromatid and isochromatid breaks and exchange figures such as dicentrics and rings. Fragments observed with an exchange figure were not scored as an aberaion but instead were considered part of the incomplete exhange. Chromatid and isochromatid gaps were recorded but not included in the anylaisis. Cells were arrested in metaphase by the addition of colcemid two hours prior to harvest. - Evaluation criteria:
- The frequency of the cells with structural chromosome aberrations in either the untreated or solvent control must be no greater than 6%. the percentage of cells with chromosome aberations in the positive control must be statistically increased relative to the untreated control.
- Statistics:
- Statistical analysis of the percent aberrant cells was performed using the Fisher's exact test. The Fisher's exact test was used to compare pairwise the percent aberrant cells of each treatment group with that of the solvent control. In the event of a positive Fisher's test article dose level, the Cochran-Armitage test was used to measure dose-responsiveness.
Results and discussion
Test results
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Reduction in mitotic index in the absence of S-9 mix only.
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: Test concentrations 150, 500, 1500 and 5000 ug/ml were pH adjusted to approximately pH 7 in treatment medium prior to addition of the treatment flasks in order to maintain the neutrality of the test system.
Any other information on results incl. tables
Cytogenetic analysis of CHO cells with isophthalic acid in the absence of exogenous metabolic activation
Treatment1 |
Flask |
Mitotic Index2(%) |
Cells Scored |
Aberrant Cells3(%) |
Total Number of Structural Aberrations |
Average Aberrations Per Cell3,7 |
||||||
Chromatid-type4 |
Chromosome-type5 |
Severely Damaged Cells6 |
||||||||||
Gaps |
Breaks |
Exch |
Breaks |
Dic |
Ring |
|||||||
Untreated cells |
A |
4.8 |
100 |
2 |
3 |
0 |
0 |
1 |
1 |
0 |
0 |
0.020 |
B |
4.6 |
100 |
2 |
1 |
1 |
0 |
1 |
0 |
0 |
0 |
0.020 |
|
DMSO |
A |
5.0 |
100 |
0 |
3 |
0 |
0 |
0 |
0 |
0 |
0 |
0.000 |
B |
4.8 |
100 |
1 |
1 |
1 |
0 |
0 |
0 |
0 |
0 |
0.010 |
|
Isophthalic acid |
||||||||||||
625 µg/ml |
A |
4.0 |
100 |
1 |
1 |
0 |
0 |
1 |
0 |
0 |
0 |
0.010 |
B |
3.6 |
100 |
2 |
0 |
1 |
0 |
1 |
0 |
0 |
0 |
0.020 |
|
1250 µg/ml |
A |
3.0 |
100 |
1 |
1 |
1 |
0 |
0 |
0 |
0 |
0 |
0.010 |
B |
3.4 |
100 |
1 |
0 |
0 |
0 |
0 |
1 |
0 |
0 |
0.010 |
|
2500 µg/ml |
A |
2.4 |
100 |
3 |
1 |
1 |
0 |
2 |
0 |
0 |
0 |
0.030 |
B |
3.0 |
100 |
3 |
1 |
2 |
0 |
1 |
1 |
0 |
0 |
0.040 |
|
5000 µg/ml |
A |
4.4 |
100 |
2 |
1 |
0 |
0 |
1 |
0 |
0 |
1 |
0.110 |
B |
4.0 |
100 |
1 |
0 |
1 |
0 |
0 |
1 |
0 |
0 |
0.020 |
|
TEM 0.5 µg/ml |
A |
2.2 |
100 |
18 |
6 |
13 |
3 |
2 |
2 |
0 |
1 |
0.300 |
B |
2.6 |
100 |
18 |
7 |
13 |
3 |
2 |
0 |
0 |
2 |
0.400 |
1 CHO cells treated for 10 hours at 37±1 °C in the absence of an exogenous source of metabolic activation.
2 Mitotic index is number mitotic figures x 100/500 cells counted.
3 Excluding cells with only gaps.
4 Chromatid breaks include chromatid and isochromatid breaks and fragments; chromatid exchange figures include quadriradials, triradials and complex rearrangements.
5 Chromosome breaks include breaks and acentric fragments; dic, dicentric chromosome.
6 Severely damaged cells includes cells with one or more pulverized chromosome and cells with 10 or more aberrations.
7 Severely damaged cells and pulverizations were counted as 10 aberrations.
Cytogenetic analysis of CHO cells with isophthalic acid in the presence of exogenous metabolic activation
Treatment1 |
Flask |
Mitotic Index2(%) |
Cells Scored |
Aberrant Cells3(%) |
Total Number of Structural Aberrations |
Average Aberrations Per Cell3,7 |
||||||
Chromatid-type4 |
Chromosome-type5 |
Severely Damaged Cells6 |
||||||||||
Gaps |
Breaks |
Exch |
Breaks |
Dic |
Ring |
|||||||
Untreated cells |
A |
8.4 |
100 |
2 |
0 |
0 |
0 |
0 |
2 |
0 |
0 |
0.020 |
B |
8.8 |
100 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0.000 |
|
DMSO |
A |
8.0 |
100 |
3 |
1 |
0 |
0 |
3 |
0 |
0 |
0 |
0.030 |
B |
9.8 |
100 |
1 |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0.010 |
|
Isophthalic acid |
||||||||||||
625 µg/ml |
A |
8.2 |
100 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0.000 |
B |
9.2 |
100 |
2 |
0 |
0 |
1 |
1 |
0 |
0 |
0 |
0.020 |
|
1250 µg/ml |
A |
9.6 |
100 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0.000 |
B |
9.4 |
100 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0.000 |
|
2500 µg/ml |
A |
9.2 |
100 |
1 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
0.010 |
B |
8.6 |
100 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0.000 |
|
5000 µg/ml |
A |
9.6 |
100 |
2 |
1 |
1 |
0 |
0 |
0 |
1 |
0 |
0.020 |
B |
9.6 |
100 |
2 |
0 |
1 |
0 |
0 |
1 |
0 |
0 |
0.020 |
|
TEM 0.5 µg/ml |
A |
2.6 |
100 |
17 |
3 |
15 |
3 |
2 |
0 |
0 |
1 |
0.300 |
B |
2.2 |
100 |
15 |
4 |
11 |
2 |
2 |
1 |
1 |
2 |
0.370 |
1 CHO cells treated for 10 hours at 37±1 °C in the presence of an exogenous source of metabolic activation.
2 Mitotic index is number mitotic figures x 100/500 cells counted.
3 Excluding cells with only gaps.
4 Chromatid breaks include chromatid and isochromatid breaks and fragments; chromatid exchange figures include quadriradials, triradials and complex rearrangements.
5 Chromosome breaks include breaks and acentric fragments; dic, dicentric chromosome.
6 Severely damaged cells includes cells with one or more pulverized chromosome and cells with 10 or more aberrations.
7 Severely damaged cells and pulverizations were counted as 10 aberrations.
Summary of results
Treatment |
S-9 Activation |
Harvest Time |
Mitotic Index |
Cells Scored |
Aberrations Per Cell1(Mean ± SD) |
Cells with Aberrations (%) |
Untreated cells |
- |
12 |
4.7 |
200 |
0.020 ± 0.140 |
2.0 |
DMSO |
- |
12 |
4.9 |
200 |
0.005 ± 0.071 |
0.5 |
Isophthalic acid |
||||||
625 µg/ml |
- |
12 |
3.8 |
200 |
0.015 ± 0.122 |
1.5 |
1250 µg/ml |
- |
12 |
3.2 |
200 |
0.010 ± 0.100 |
1.0 |
2500 µg/ml |
- |
12 |
2.7 |
200 |
0.035 ± 0.210 |
3.0 |
5000 µg/ml |
- |
12 |
4.2 |
200 |
0.065 ± 0.723 |
1.5 |
TEM 0.5 µg/ml |
- |
12 |
2.4 |
200 |
0.350 ± 1.291 |
18.0** |
|
||||||
Untreated cells |
+ |
10 |
8.6 |
200 |
0.010 ± 0.100 |
1.0 |
DMSO |
+ |
10 |
8.9 |
200 |
0.020 ± 0.140 |
2.0 |
Isophthalic acid |
||||||
625 µg/ml |
+ |
10 |
8.7 |
200 |
0.010 ± 0.100 |
1.0 |
1250 µg/ml |
+ |
10 |
9.5 |
200 |
0.000 ± 0.000 |
0.0 |
2500 µg/ml |
+ |
10 |
8.9 |
200 |
0.005 ± 0.071 |
0.5 |
5000 µg/ml |
+ |
10 |
9.6 |
200 |
0.020 ± 0.140 |
2.0 |
CP 50 µg/ml |
+ |
10 |
2.4 |
200 |
0.335 ± 1.293 |
16.0** |
1 Severely damaged cells were counted as 10 aberrations
** p≤0.01 Fisher’s exact test
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of the assay described in this report, isophthalic acid was concluded to be negative under the conditions of this study
- Executive summary:
The potential clastogenicity of isophthalic acid was investigated in vitro in CHO cells. Duplicate cultures were exposed to the test material (in DMSO) in the presence and absence of an exogenous metabolic activation system (Aroclor 1254 -induced male Sprague-Dawley rat liver S9 fraction) at concentrations of 625, 1250, 2500 and 5000 µg/ml. Cells were arrested in metaphase by the addition of Colcemid two hours prior to harvest. Cells were exposed for 10 hours (-S9) or 2 hours (+S9) and harvested after 12 hours (-S9) or 10 hours (+S9) and 100 cells/duplicate flask assessed for chromosomal aberrations. Exposure to the test material did not result in any significant increase in the levels of chromosomal aberrations; appropriate responses were seen with the positive control compounds TEM and CPS. No evidence of clastogenicity was seen under the conditions of this study.
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