Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 607-813-5 | CAS number: 25830-77-7
- 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:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 24 May 2016 - 15 June 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 016
- Report date:
- 2016
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- 2010
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- #440/2008, including most recent amendments
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2600 (Skin Sensitisation)
- Version / remarks:
- 2003
- Deviations:
- no
- GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- 2-[(3S)-2,6-dioxooxan-3-yl]isoindole-1,3-dione
- EC Number:
- 607-813-5
- Cas Number:
- 25830-77-7
- Molecular formula:
- C13 H9 N O5
- IUPAC Name:
- 2-[(3S)-2,6-dioxooxan-3-yl]isoindole-1,3-dione
- Test material form:
- solid
- Details on test material:
- - Appearance: white solid
- Storage conditions: in refrigerator (2-8°C) protected from light
Constituent 1
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- CBA:J
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Females (if applicable) nulliparous and non-pregnant: yes
- Microbiological status of animals, when known: SPF
- Age at study initiation: ca. 10 weeks
- Weight at study initiation: 18.6-24.5 g
- Housing: group housed in labeled Makrolon cages (MIII type; height 18 cm) containing sterilised sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany). Paper (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom) and shelters (disposable paper corner home, MCORN 404, Datesand Ltd, USA) were supplied as cage-enrichment. On Day 6, the animals were group housed in Makrolon MII type cages with a sheet of paper instead of sawdust and cage enrichment.
- Diet (e.g. ad libitum): pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days
- Indication of any skin lesions: the ears were intact and free from any abnormality.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): set to maintain 18-24
- Humidity (%): set to maintain 40-70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12
- IN-LIFE DATES: From: 24 May 2016 To: 15 June 2016
Study design: in vivo (LLNA)
- Vehicle:
- dimethylformamide
- Concentration:
- 0 (vehicle controls), 10, 25 and 50%
- No. of animals per dose:
- Main study: 5 females/dose
Pre-screen: 2 females/dose - Details on study design:
- PRE-SCREEN TESTS:
- Compound solubility: soluble in N,N-dimethylformamide to at least 50% (maximal concentration required by the guideline)
- Irritation: No irritation was observed
- Systemic toxicity: No signs of systemic toxicity were noted
- Ear thickness measurements: Ear thickness measurements were conducted using a digital thickness gauge (Kroeplin C110T-K) prior to dosing on Days 1 and 3, and on Day 6. Variations in ear thickness during the observation period were less than 25% from Day 1 pre-dose values. White test item remnants were present on the dorsal surface of the ears of both animals at 25% and 50% (between Days 1 and 4), which did not hamper scoring of the skin reactions.
- Erythema scores: 0 at all time points in all animals
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response: DPM values are presented for each animal and for each dose group. A Stimulation Index (SI) is calculated for each group using the individual SI values. The individual SI is the ratio of the DPM/animal compared to the DPM/vehicle control group mean. If the results indicate a SI ≥ 3, the test item may be regarded as a skin sensitizer.
TREATMENT PREPARATION AND ADMINISTRATION:
The vehicle was selected on the basis of maximizing the solubility using the test item data provided by the Sponsor and trial preparation results performed at Charles River Den Bosch. The test item preparations (w/w) were prepared within 4 hours prior to each dosing. No adjustment was made for specific gravity of the vehicle. Homogeneity was assessed by visual inspection of the solutions. Correction of the purity/composition of the test item is not applicable, since the test method requires a logical concentration range rather than specific dose levels to be dosed.
The dorsal surface of both ears was topically treated (25 μL/ear) with the test item, at approximately the same time on each day. The concentrations were stirred with a magnetic stirrer immediately prior to dosing.
The control animals were treated in the same way as the experimental animals, except that the vehicle was administered instead of the test item.
On day 6, each animal was injected via the tail vein with 0.25 mL of sterile phosphate buffered saline (PBS) (Merck, Darmstadt, Germany) containing 20 μCi of 3H-methyl thymidine (PerkinElmer Life and Analytical Sciences, Boston, MA, US). After five hours, all animals were killed by intraperitoneal injection (0.2 mL/animal) of Euthasol® 20% (AST Farma BV, Oudewater, The Netherlands). The draining (auricular) lymph node of each ear was excised. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- Not performed
Results and discussion
- Positive control results:
- The results of a reliability test with three concentrations of Hexylcinnamaldehyde (CAS No. 101-86-0) in Acetone/Olive oil (4:1 v/v), performed not more than 6 months previously and using the same materials, are available and confirm the validity of the study.
In vivo (LLNA)
Resultsopen allclose all
- Key result
- Parameter:
- SI
- Value:
- 12
- Variability:
- ± 2.0
- Test group / Remarks:
- 10%
- Key result
- Parameter:
- SI
- Value:
- 5.9
- Variability:
- ± 1.1
- Test group / Remarks:
- 25%
- Key result
- Parameter:
- SI
- Value:
- 5.2
- Variability:
- ± 1.4
- Test group / Remarks:
- 50%
- Key result
- Parameter:
- SI
- Value:
- 1
- Variability:
- ± 0.2
- Test group / Remarks:
- 0% (vehicle controls)
- Key result
- Parameter:
- SI
- Value:
- 4.4
- Variability:
- ± 0.9
- Test group / Remarks:
- 25% alpha-hexylcinnamaldehyde (reliability check, positive control)
- Cellular proliferation data / Observations:
- CELLULAR PROLIFERATION DATA
Mean DPM/animal values for the experimental groups treated with test item concentrations 10, 25 and 50% were 9361, 4624 and 4054 DPM, respectively. The mean DPM/animal value for the vehicle control group was 780 DPM. The DMP/animal value in the reliability check with 25% alpha-hexylcinnamaldehyde was 4551 ± 643.
DETAILS ON STIMULATION INDEX CALCULATION
DPM values are presented for each animal and for each dose group. A Stimulation Index (SI) is calculated for each group using the individual SI values. The individual SI is the ratio of the DPM/animal compared to the DPM/vehicle control group mean.
The response did not follow the expected dose-response relationship, more often seen in these kind of studies. The response of the mid and high dose groups might be less due to differences in skin penetration (less vehicle present).
EC3 CALCULATION
The EC3 value (the estimated test item concentration that will give a SI =3) was established to be between >0 and 10%.
CLINICAL OBSERVATIONS:
No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study.
BODY WEIGHTS
Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.
Any other information on results incl. tables
The majority of auricular lymph nodes across all test item treated groups were considered slightly enlarged. No macroscopic abnormalities of the surrounding area were noted for any of the animals.
Applicant's summary and conclusion
- Interpretation of results:
- Category 1 (skin sensitising) based on GHS criteria
- Conclusions:
- In a GLP-compliant guideline study, the test substance induced the Stimulation Indices of 12.0, 5.9 and 5.2 as 10%, 25% and 50% solution in dimethylformamide, respectively. Based on the results of the study the substance is considered to be sensitizing to skin.
- Executive summary:
In a GLP-compliant OECD Guideline 429 study (LLNA assay), the test substance at concentrations 10%, 25% and 50% solution in dimethylformamide induced the Stimulation Indices of 12.0, 5.9 and 5.2. Mean DPM/animal values for the experimental groups treated with test item concentrations 10, 25 and 50% were 9361, 4624 and 4054 DPM, respectively. The mean DPM/animal value for the vehicle control group was 780 DPM. No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period. The majority of auricular lymph nodes across all test item treated groups were considered slightly enlarged. No macroscopic abnormalities of the surrounding area were noted for any of the animals. The validity of the study was confirmed by reliability check with Alpha-hexylcinnamaldehyde performed not more than 6 months previously at the same test facility. The mean DPM/animal value for 25% alpha-hexylcinnamaldehyde was 4551 ± 643. The respective Stimulation Index was calculated to be 4.4. Based on the results of the study, the test substance is considered to be sensitizing to skin under the conditions of the assay and should be classified as Skin Sens. 1, H317 under Regulation 1272/2008/EC.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.