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EC number: 204-635-6 | CAS number: 123-56-8
- 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:
- 2004-04-13 to 2004-06-07
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 004
- Report date:
- 2004
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- adopted 24 April 2002
- Deviations:
- no
- GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- Succinimide
- EC Number:
- 204-635-6
- EC Name:
- Succinimide
- Cas Number:
- 123-56-8
- Molecular formula:
- C4H5NO2
- IUPAC Name:
- pyrrolidine-2,5-dione
- Details on test material:
- - Name of test material: Succinimide
- Chemical name: 2,5-Diketopyrrolidine
- Physical state: CWhite scalls
- Batch No.: SSGS 029
- Solubility: in water 330 g/L at 20 °C
- Melting point: 123 - 125 !C
- Storage condition of test material: Dark , usage under light possible.
- Stability at conditions of storage: Stable.
- Stability in solutions: Stable.
- Date of expiry: 30 June 2005.
Constituent 1
- Specific details on test material used for the study:
- TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test substance was solved in DMSO
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- CBA
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Species, strain: Mice, CBA/CaOlaHsd
- Supplier: Harlan Winkelman GmbH, D-33176 Borchen
- Sex, specification: Females, healthy young adult nulliparous animals
- Age of the animals: About 8 weeks at the first administration
- Weight range of the animals at the first application: 16.2 - 22.9 g
- Spare animals: The 5th animal of each group served as spare animal. It was treated in the same way as the other animals of its group
Since all animals survived and all animals received the correct amount of 3HTdR all spare-animals were taken for the examination of the results.
ENVIRONMENTAL CONDITIONS
- Hygiene: Optimal hygienic conditions
- Room temperature: Average of 22.0 °C (continuous monitoring and recording)
- Relative humidity: Average of 44.4 % (continuous monitoring and recording)
- Light: Only artificial light from 6.00 a.m. to 6.00 p.m.
- Cages: Single caging. Makrolon cages type II, (22 cm x 16.5 cm ground area, 15 cm high)
- Feed: Altromin maintenance diet for rats and mice, item No. 1324forte, ad libitum
- Water: Tap water from Makrolon-bottles with stainless steel canules, ad libitum
- Bedding material: Aspen wood chips, ABEDD, Dominik Mayr KEG, A-8580 Köflach
Germ reduction by autoclaving
- Identification of animals: by shearing a defined for region on the back of the animal and by cage tag
- Acclimatisation: 6 days
Study design: in vivo (LLNA)
- Vehicle:
- dimethyl sulphoxide
- Concentration:
- •Group A (low dose): 10 % (w/w) in DMSO
•Group B (mid dose): 25 % (w/w) in DMSO
•Group C (high dose): 46.1 % (w/w) in DMSO
•Group P (positive control): 25% (v/v) solution of hexyl cinnamic aldehyde (technical grade, 85%) in acetone:olive oil (4:1, v/v)
•Group K (negative control): DMSO - No. of animals per dose:
- 5
- Details on study design:
- RANGE FINDING TESTS:
A range finding study was performed with two animals/concentration with following concentrations: 46.1 % and 25 % (46.1 % is the maximal achievable concentration suitable for application). In this study the animals were treated in the same manner as in a main study with 25 µL test substance on the dorsum of each ear on three consecutive days. Ear thickness and body weight were measured on Day 1 before the first administration and on Day 4 about 24 hours after the last administration.
None of the animals showed overt systemic toxicity or excessive local skin irritation. The observed little increase in ear thickness is known from our experience within the normal range and does indicate slight irritation at the most. Therefore, 46.1% was chosen as highest test substance concentration and ear thickness measurement was not performed in the main study.
MAIN STUDY
Bias control
The individual animals were allocated to their groups by random numbers.
Test design
The test substance was administered in 3 concentrations to the dorsal surfaces of the ears of the animals of the test substance groups. In a manner identical to that of animals in the treatment groups animals of one negative control group and one positive control group were treated with DMSO and hexyl cinnamic aldehyde, respectively. Each animal was treated for 3 consecutive days. 3 days after the last administration the proliferation of the lymphocytes of the draining lymph nodes was measured by the determination of the amounts of incorporated 3HTdR.
Incorporation of 3H-methyl thymidine in vivo
5 days after the first topical administration, each animal received 20 µCi 3HTdR by slow intravenous administration. The injection solution containing nominal 80 µCi/mL 3HTdR was prepared by the dilution of 1.152 mL 3HTdR (amersham pharmacia biotech, Kat. Nr.: TRA 310, batch B314, specific activity 2.0 Ci/mmol, radioactive concentration 1 mCi/mL, radiochemical purity 99.0 %, thymine content 0.1 %) with 13.248 mL PBS. Several minutes prior to 3HTdR administration the animals were kept restrained in Plexiglas-tubes and the tail veins were visualised by placing the tails in warm water. Then 250 µL of the injection solution were intravenously administered to each animal.
Preparation of single cell suspensions and determination of incorporated 3H-methyl thymidine
Approximately 5 hours after 3HTdR injection all animals were sacrificed by carbon dioxide asphyxiation and the draining auricular lymph nodes were rapidly excised. The lymph nodes of each group were pooled in PBS. A single cell suspension (SCS) of lymph node cells (LNC) was prepared by gentle mechanical disaggregation of the pooled lymph nodes through a 70 µm cell strainer. The SCSs were then transferred into centrifuge tubes and LNC were pelleted by centrifugation (4 °C, max. 200 g, 10 min). Afterwards supernatants were removed by aspiration. Then the LNC were resuspended and washed twice with PBS. After the final washing the supernatants were removed leaving just a small volume (<0.5 mL) and macromolecules were precipitated by incubation with 5 % trichloroacetic acid (TCA) at 4°C overnight. Each precipitate was pelleted by centrifugation (4 °C, max. 200 g, 10 min) and resuspended in 1 mL TCA. This suspension was transferred into scintillation vials containing 10 mL scintillation cocktail (Packard Bioscience: Ultima Gold, order no. 6013329) and 3HTdR incorporation was determined with a beta-scintillation counter (TriCarb 2200CA, Packard Instrument Co., protocol 4: single label 3H, dpm, AEC-quenchcurve in Ultima Gold from 21 June 2002). - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
Results and discussion
- Positive control results:
- Application of 25% HCA in AOO resulted in an SI of 5.0.
This result proves the sensitivity of the strain of animals used and the reliability of the experimental technique.
In vivo (LLNA)
Resultsopen allclose all
- Parameter:
- SI
- Value:
- 0.7
- Test group / Remarks:
- Group A (low dose) 10% w/w test substance, 5 females
- Parameter:
- SI
- Value:
- 0.7
- Test group / Remarks:
- Group B (mid dose) 25% w/w test substance, 5 females
- Parameter:
- SI
- Value:
- 0.4
- Test group / Remarks:
- Group C (high dose) 46.1% w/w test substance, 5 females
- Parameter:
- SI
- Value:
- 5
- Test group / Remarks:
- Group P (positive control), 5 females
- Parameter:
- SI
- Value:
- 1
- Test group / Remarks:
- Group K (negative control), 5 females
- Cellular proliferation data / Observations:
- DETAILS ON STIMULATION INDEX CALCULATION: Results are presented as test/control ratio (Stimulation index), calculated as dpm test group/dpm negative control group.
(dpm = disintegrations per minute, corrected by the subtraction of the background)
A substance is regarded as a sensitiser in the LLNA if the test substance induces a 3-fold or greater increase in 3HTdR incorporation into lymph node cells of test lymph nodes relative to that recorded for control lymph nodes, as indicated by the SI, together with the consideration of dose response.
The Sl of the test substance groups were between 0.4 and 0.7.
CLINICAL OBSERVATIONS:
No abnormal behaviour or clinical signs were detected during the experiment in the animals. No local irritations were observed at the application sites of all animals of all test substance groups and the negative control group throughout the whole study. On Days 2-5 all animals of the positive control group had moderate erythema on the application sites indicating slight irritative skin reactions.
BODY WEIGHTS:
Body masses and body mass gain of all animals were in the range to be expected from animals of the same strain, sex and age. Body weight loss was noted in 1/5 animals in group A and C. On Day 1 the body mass of one animal of group C (22.9g) exceeded a little bit over the 20%of the mean weight (mean body mass + 20%: 22.5g) which is not of relevance for the obtained results.
POSITIVE CONTROL: Application of 25% HCA in AOO resulted in an SI of 5.0. This result proves the sensitivity of the strain of animals used and the reliability of the experimental technique.
Any other information on results incl. tables
Table 1. Disintegrations per minute and calculated SI
dpm | SI | |
Group K (negative control) | 8861 | 1 |
Group A (low dose) | 6536 | 0.7 |
Group B (mid dose) | 6127 | 0.7 |
Group C (high dose) | 2242 | 0.4 |
Group P (positive control) | 44,360 | 5.0 |
dpm = disintegrations per minute
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Remarks:
- Migrated information
- Conclusions:
- "Succinimide" is regarded as a non sensitiser in the LLNA according to OECD-Guideline 429, since the SI of all examined test substance concentrations were clearly smaller than 3.
- Executive summary:
In a dermal skin sensitisation study conducted according to OECD guideline 429 (Local Lymph Node Assay) with succinimide dissolved in DMSO at concentrations of 10% (w/w), 25% (w/w) and 46.1% (w/w), young adult female CBA/CaOlaHsd mice were tested. The test substance was solved in DMSO and was administered to three groups of 5 female CBA/Ca mice. Administration was performed epicutaneously to the dorsal surface of both ears, once a day on three consecutive days. The volume administered was 25 µL per ear. A 25% (v/v) solution of hexyl cinnamic aldehyde in acetone:olive oil (4:1, v/v) was used a positive control. All animals survived till the end of the study. No adverse effects were noted in any animal. Body mass and body mass gain was in the range to be expected from animals of the same strain, sex and age. Moderate erythema was noted in all animals of the positive control group on Days 2-5, indicating slight local skin irritation. No skin irritating effects were observed in the test substance groups and the negative control group throughout the whole study. The SI of the tested test substance concentrations were 0.7 (low dose), 0.7 (mid dose) and 0.4 (high dose). The positive control substance led to a stimulation index of 5.0, thus demonstrating the validity of the experiment.
In this study, succinimide is not a dermal sensitiser according to CLP criteria.
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