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EC number: 940-877-5 | CAS number: -
- 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
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Endpoint summary
Administrative data
Description of key information
LLNA: not sensitising
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 07 Mar - 30 Mar 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- adopted in 2010
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Landesinstitut für Arbeitsschutz und Produktsicherheit, München, Germany
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- other: CBA/CaOlaHsD
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Harlan Winkelmann, Borchen, Germany
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 18-23 g
- Fasting period before study: no
- Housing: single housing in IVC cages, type II L
- Diet: Altromin 1324 maintenance diet for rats and mice (Lot No. 1114), ad libitum
- Water: tap water (sulphur acidified to a pH of 2.8), ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 55±10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12 - Vehicle:
- dimethyl sulphoxide
- Concentration:
- 6.25%, 12.5%, and 25% (w/v)
- No. of animals per dose:
- 5
- Details on study design:
- RANGE FINDING TESTS:
2 animals were treated by topical application with the test item on 3 consecutive days at a concentration of 25% (suspended in DMSO) to the entire dorsal surface of the ear. Immediately before the first application, 48 h thereafter and shortly before sacrificing the thickness of both ears of all animals was measured. No signs of systemic toxicity or signs of irritation at the application site were detected. The measurement of ear thickness revealed no difference between control and treated animals and no change of ear thickness was observed at the different time points. All animals showed the expected body weight development throughout the duration of the preliminary test. The maximum technically applicable concentration in the vehicle was 25%.
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: 3H-methyl thymidine incorporation (determined by beta-scintillation).
- Criteria used to consider a positive response: A substance will be regarded as a 'sensitiser' in the LLNA if at least one concentration of the test item results in a 3-fold or greater increase in 3H-methyl thymidine-incorporation into lymph node cells of the test group animals relative to that recorded for the lymph nodes of control group animals (SI ≥ 3).
TREATMENT PREPARATION AND ADMINISTRATION:
Each mouse was treated by topical application of 25 µL of the selected solution to the entire dorsal surface of each ear. Topical applications were performed once daily over three consecutive days.
Five days after the first topical application all mice were dosed with 250 µL 3H-methyl thymidine (corresponding to 20 µCi) by intravenous injection (tail vein).
Approximately 5 hours after the injection of 3H-methyl thymidine all mice were sacrificed by cervical dislocation. The draining auricular lymph nodes were excised, individually pooled for each animal (2 lymph nodes per animal) and collected with phosphate buffered saline (PBS). A single cell suspension of pooled lymph node cells was prepared by gentle mechanical disaggregation through polyamide gauze (200 mesh size). After washing the gauze with PBS the cell suspension was pelleted in a centrifuge. The supernatant was discarded and the pellets were resuspended with PBS. This washing procedure was repeated.
After the final wash each pellet was resuspended in approximately 1 mL 5% TCA at 4°C for approximately 18 hours for precipitation of macromolecules. Each precipitate was once washed again, resuspended in 1 mL 5% TCA and 7 mL scintillation fluid was added. Then this solution was transferred into scintillation vials and stored at room temperature overnight.
The 3H-methyl thymidine–incorporation was measured in a ß-counter and expressed as the number of disintegrations per minute (DPM). Similarly, background 3H-methyl thymidine levels were also measured (5% TCA). Determination of radioactivity was performed individually for each animal. - Positive control substance(s):
- other: p-phenylendiamine (CAS 106-50-3, 1% on three consecutive days; reliability check in February 2012)
- Positive control results:
- The positive control substance p-phenylendiamine induced an SI of 9.8 ± 3.8 (5 animals).
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: Values are given as mean ± SD Control: 3392 ± 1024 6.25%: 3848 ± 1312 12.5%: 2988 ± 920 25%: 2268 ± 574
- Key result
- Parameter:
- SI
- Value:
- 1.1
- Variability:
- ± 0.4
- Test group / Remarks:
- 6.25%
- Key result
- Parameter:
- SI
- Value:
- 0.9
- Variability:
- ± 0.3
- Test group / Remarks:
- 12.5%
- Key result
- Parameter:
- SI
- Value:
- 0.7
- Variability:
- ± 0.2
- Test group / Remarks:
- 25%
- Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
- Conclusions:
- CLP: not classified
Reference
No effects on the body weight development were observed.
Table 1: DPM and stimulation index of the LLNA.
Concentration |
Animal No. |
DPM |
Stimulation index |
6.25% |
1 |
2990 |
|
|
2 |
4336 |
|
|
3 |
4269 |
|
|
4 |
1891 |
|
|
5 |
5754 |
|
|
Mean ± SD |
3848 ± 1312 |
1.1 ± 0.4 |
12.5% |
6 |
2260 |
|
|
7 |
4387 |
|
|
8 |
1953 |
|
|
9 |
2617 |
|
|
10 |
3726 |
|
|
Mean ± SD |
2988 ± 920 |
0.9 ± 0.3 |
25% |
11 |
2916 |
|
|
12 |
2278 |
|
|
13 |
1563 |
|
|
14 |
2897 |
|
|
15 |
1688 |
|
|
Mean ± SD |
2268 ± 574 |
0.7 ± 0.2 |
Negative control |
16 |
2654 |
|
|
17 |
2543 |
|
|
18 |
2557 |
|
|
19 |
4188 |
|
|
20 |
5019 |
|
|
Mean ± SD |
3392 ± 1024 |
1.0 |
Background (scintillation fluid and trichloroacetic acid) |
|
14 |
|
|
|
14 |
|
|
|
19 |
|
|
|
32 |
|
|
|
12 |
|
|
Mean ± SD |
18 ± 7 |
0.0 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
A study performed according to OECD guideline 429 and in compliance with GLP, is available for assessment of skin sensitizing properties of Reaction mass of 2-(3,4-dimethyl-1H-pyrazol-1-yl)succinic acid and 2-(4,5-dimethyl-1H-pyrazol-1-yl)succinic acid (Lütkenhaus, 2012). Five CBA mice per dose were treated with 25 µl of 6.25%, 12.5%, and 25% test substance (diluted in DMSO) once daily for 3 consecutive days. The dosing concentrations were determined in a range-finder assay. No signs of systemic toxicity or signs of irritation at the application site were detected after treatment of the animals with up to 25% test item solution. 25% was the maximum technically applicable concentration determined in a solubility test. Five days after the first topical application all mice were dosed with 250 µL 3H-methyl thymidine (corresponding to 20 µCi) by intravenous injection (tail vein). Approximately 5 hours after the injection of 3H-methyl thymidine all mice were sacrificed by cervical dislocation. The draining auricular lymph nodes were excised, individually pooled for each animal (2 lymph nodes per animal) and collected with phosphate buffered saline (PBS). A single cell suspension of pooled lymph node cells was prepared and washed. After precipitation of macromolecules with TCA, scintillation fluid was added and the 3H-methyl thymidine–incorporation was measured in a ß-counter and expressed as the number of disintegrations per minute (DPM). Similarly, background 3H-methyl thymidine levels were also measured (5% TCA). Determination of radioactivity was performed individually for each animal.
The DPM were 3392±1024, 3848±1312, 2988±920, and 2268±574 for the control, 6.25%, 12.5%, and 25% dose group, respectively. The resulting stimulation indices were 1.1 ± 0.4, 0.9 ± 0.3 and 0.7 ± 0.2 for the 6.25%, 12.5%, and 25% dose group, respectively. In addition, no signs of systemic toxicity or signs of irritation at the application site were detected. In conclusion, as the stimulation index after treatment with Reaction mass of 2-(3,4-dimethyl-1H-pyrazol-1-yl)succinic acid and 2-(4,5-dimethyl-1H-pyrazol-1-yl)succinic acid was smaller than three, the test item was not sensitising under the conditions of the test.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
The available data on skin sensitisation of Reaction mass of 2-(3,4-dimethyl-1H-pyrazol-1-yl) succinic acid and 2-(4,5-dimethyl-1H-pyrazol-1-yl) succinic acid do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.
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.
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