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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
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- migrated information: read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- 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:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
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:
- ZAN 573. Lot 130072591. yellow to brown course powder. molecular weight: 424.314 g/m. 100% purity. Expiry date: 24 January 2016.
Constituent 1
Constituent 2
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- CBA
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: CBA/J Rj mice, ELEVAGE JANVIER, Route des Chènes Secs B.P. 4105 53940 LE GENEST-ST-ISLE, France
- Age at study initiation: 9 weeks
- Weight at study initiation: 19.8-21.9 g
- Housing: Type II. polypropylene / polycarbonate, Lignocel3/4-FASERN Hygienic Animal Bedding available
- Diet (e.g. ad libitum): ssniff SM Rat/Mouse – “Breeding & Maintenance", ad libitum
- Water (e.g. ad libitum): tap water from the municipal supply from 500 mL bottle, ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.0-26.8
- Humidity (%): 33-79
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: To:
Study design: in vivo (LLNA)
- Vehicle:
- dimethylformamide
- Concentration:
- 50% solution in DMF
- No. of animals per dose:
- 4
- Details on study design:
- RANGE FINDING TESTS:
- Compound solubility: soluble in DMF at a maximum of 50% (w/v), forming a brown transparent solution. Doses of 50%, 25% and 10% (w/v) were used in the preliminary study.
- Irritation: All animals scratched at the dosage sites on day 1, and alopecia was observed at the 50% dose group on d 2-6 and in the 25% dose group on days 3-6. No significant increase in ear thickness was seen, nor was there any indication of irritation at the site of application.
- Lymph node proliferation response: the draining lymph nodes were visually examinate dan the appearance was normal in all animals.
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response: The test item is regarded as a sensitizer if both of the following criteria are fulfilled:
That exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than recorded in control mice, as indicated by the stimulation index.
The data are compatible with a conventional dose response, although allowance must be made (especially at high topical concentrations) for either local toxicity or immunological suppression.
The Local Lymph Node Assay is considered valid if it meets the following criteria:
- the DPN value of the negative (vehicle) control group falls within the range of historical laboratory control data,
- the positive control substance produces a significant lymphoproliferative response increases (SI>3),
- each treated and control group includes at least 4 animals,
- the test item does not cause serious systemic or local toxicity.
TREATMENT PREPARATION AND ADMINISTRATION:
Animals were topically dosed with 25 µL of the appropriate formulation using a pipette on the dorsal surface of each ear. Each animal was dosed once a day for three consecutive days (Days 1, 2 and 3). Each animal was observed daily for any clinical signs, including local irritation and systemic toxicity. Clinical observations were performed at least twice a day on Days 1, 2 and 3 and once daily on Days 4, 5 and 6. Individual records were maintained.
Individual body weights were recorded on Day 1 (beginning of the test) and on Day 6 (prior to 3HTdR injection) with a precision of ± 0.1 g.
Both ears of each mouse were observed for erythema and ear thickness was measured using a thickness gauge on Day 1 (pre-dose), Day 3 (approximately 48 hours after the first dose) and Day 6. Additional quantification of the ear thickness was performed by ear punch weight determination after the euthanasia of the experimental animals.
On Day 6, animals were intravenously injected via the tail vein with 250 µL of sterile PBS containing approximately 20 µCi of 3HTdR. Once injected, the mice were left for 5 hours (± 30 minutes). The mice were euthanized by asphyxiation with ascending doses of carbon dioxide. The draining auricular lymph nodes were excised and the nodes of mice from each test group were pooled and collected in separate Petri dishes containing a small amount (1-2 mL) of PBS. A single cell suspension (SCS) of pooled lymph node cells (LNCs) was prepared and collected in disposable tubes by gentle mechanical disaggregation. Pooled LNCs were pelleted with a relative centrifugal force (RCF) of 190 x g (approximately) for 10 minutes at 4 degrees C. Pellets were gently resuspended and
washed twice. The pellets were finally resuspended in 3 mL of 5% (w/v) TCA solution. After overnight incubation at 2-8 degrees C, precipitates were centrifuged and pellets were resuspended in TCA solution and dispersed by using an ultrasonic bath. Samples were transferred into a suitable sized scintillation vial filled with 10 mL of scintillation liquid and thoroughly mixed. The vials were loaded into a β-scintillation counter and 3HTdR incorporation was measured (10-minute measurement) of decays per minute. Background DPM level was also measured in duplicates by adding 1 mL of 5% (w/v) TCA solution into a scintillation vial filled with 10 mL of scintillation liquid. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- DPM was measured for each pooled group of nodes. The measured DPM values were corrected with the background DPM value (“DPM”). The average of the two measured DPM values of 5% (w/v) TCA solutions was used as background DPM value. The results were expressed as “DPN” (DPM divided by the number of lymph nodes) following the industry standard for data presentation.
Stimulation index (SI = DPN value of a treated group divided by the DPN value of the negative control group) for each treatment group was calculated. A stimulation index of 3 or greater is an indication of a positive result.
The EC3 value of the test item (= concentration of test item which results in a SI of 3) was calculated. The calculation of the EC3 value was conducted by linear interpolation according to the equation: EC3 = c + [(3-d)/(b-d)] x (a-c)
where the data points lying immediately above and below the SI value of 3 on the LLNA dose-response plot have the co-ordinates (a,b) and (c,d) respectively.
Results and discussion
In vivo (LLNA)
Resultsopen allclose all
- Parameter:
- SI
- Remarks on result:
- other: The stimulation indices for the test material at 50%, 25%, 10% and 2% (w/v) dilution were 24.4, 16.8, 13.3 and 2.9.
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: Net DPMs in the vehicle control, 50%, 25%, and 10% were 3259.5, 79656.5, 54843.5, 43335.5, respectively. In a second experiment, the vehicle control was 240.9 and the 2% test item was 695.6 DPM.
Any other information on results incl. tables
No mortality or signs of systemic toxicity were observed during the study. There was no significant change in body weights between the dose groups. A minimal amount of test item precipitate was observed on the ears of the animals in the 50% (w/v) dose group on Day 2. All animals scratched the application side on day 1, and some alopecia was observed on day 2 (50% group) and day 3 (25% group).
DPM, DPN and Stimulation Index Values for all Groups (Experiment.1)
Test GroupName |
Measured DPM /group |
DPM |
Number of lymphnodes |
DPN |
Stimulation Index |
Background (5% (w/v) TCA) |
74 31 |
- |
- |
- |
- |
Negative (vehicle) control( DMF) |
3312 |
3259.5 |
8 |
407.4 |
1.0 |
ZAN573 (50% (w/v) in DMF) |
79709 |
79656.5 |
8 |
9957.1 |
24.4 |
ZAN573 (25% (w/v) in DMF) |
54896 |
54843.5 |
8 |
6855.4 |
16.8 |
ZAN573 (10% (w/v) in DMF) |
43388 |
43335.5 |
8 |
5416.9 |
13.3 |
Positive control (25% (w/v) HCA inDMF) |
21385 |
21332.5 |
8 |
2666.6 |
6.5 |
DPM, DPN and Stimulation Index Values for Additional Dose Group (Experiment 2)
Test Group Name |
Measured DPM/ group |
DPM |
Numberoflymphnodes |
DPN |
Mean DPM/group |
Stimulation Index |
Background(5% (w/v)TCA) |
31 32 |
- |
- |
- |
- |
- |
Negative (vehicle) control (DMF) |
477 |
445.5 |
2 |
222.8 |
240.9 |
1.0 |
462 |
430.5 |
2 |
215.3 |
|||
687 |
655.5 |
2 |
327.8 |
|||
636 |
604.5 |
2 |
302.3 |
|||
304 |
272.5 |
2 |
136.3 |
|||
ZAN573 (2% (w/v) in DMF) |
5599 |
5567.5 |
8 |
695.9 |
695.9 |
2.9 |
Positive control (25% (w/v) HCA in DMF) |
2061 |
2029.5 |
2 |
1014.8 |
1506.6 |
6.3 |
1654 |
1622.5 |
2 |
811.3 |
|||
4185 |
4153.5 |
2 |
2076.8 |
|||
2921 |
2889.5 |
2 |
1444.8 |
|||
4402 |
4370.5 |
2 |
2185.3 |
Applicant's summary and conclusion
- Interpretation of results:
- sensitising
- Remarks:
- Migrated information meets classification criteria for 1B or 1A (residual) Criteria used for interpretation of results: EU
- Conclusions:
- In an LLNA study, ZAN 573 shows a Stimulation Index above 3, and so is concluded to be skin sensitiser. The calculated EC3 value is 2.1% (w/v). Based on this value, the test item is classified as skin sensitizer Category 1 (sub-category 1B). The presence of trimellitic anhydride as a residual indicates the substance should be classified as sub-category 1A. This study is informative for evaluation of the toxicity of members of the cyclic acid anhydride chemical 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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