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EC number: 224-923-5 | CAS number: 4553-62-2
- 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:
- From 19 February 2010 to 22 March 2010
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Well conducted GLP guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 010
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- Principles of method if other than guideline:
- Not applicable.
- GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- Methyl-2-glutaronitrile
- IUPAC Name:
- Methyl-2-glutaronitrile
- Reference substance name:
- 2-methylglutaronitrile
- EC Number:
- 224-923-5
- EC Name:
- 2-methylglutaronitrile
- Cas Number:
- 4553-62-2
- Molecular formula:
- C6H8N2
- IUPAC Name:
- 2-methylpentanedinitrile
- Details on test material:
- - Name of test material (as cited in study report): Methyl-2-glutaronitrile
- Physical state: colorless liquid
- Storage condition of test material: at room temperature
Constituent 1
Constituent 2
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- other: CBA/J
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: 11-12 weeks old (preliminary study) and 11 weeks old (main study)
- Weight at study initiation: 22.3 +/- 1.0 g.
- Housing: individually
- Diet (e.g. ad libitum): SSNIFF R/M-H pelleted maintenance diet (SSNIFF Spezialdiäten GmbH, Soest, Germany)
- Water (e.g. ad libitum): Tap water filtered using a 0.22 micron filter, contained in bottles.
- Acclimation period: at least 5 days before the beginning of the study.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 30 to 70%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h (7:00 - 19:00
IN-LIFE DATES: From: 23 February 2010 To: 08 March 2010
Study design: in vivo (LLNA)
- Vehicle:
- dimethylformamide
- Remarks:
- Batch No. 00442CJ (Aldrich, Saint Quentin Fallavier, France).
- Concentration:
- 0, 5, 10, 25, 50 and 100%
- No. of animals per dose:
- 4 females per dose for the main test
- Details on study design:
- RANGE FINDING TESTS:
To assess the irritant potential of the test item (through ear thickness measurement), a preliminary test was performed on a small number of animals, as follows:
• the test item was prepared at the concentrations of 10, 25, 50 and 100%,
• for 3 consecutive days, the animals received applications of 25 µL of the dosage form preparations to the external surface of both ears (one concentration per ear),
• measurement of the ear thickness (using a micrometer) was performed each day before treatment and 72 hours after the last application
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Allocation to group: hand procedure
- Criteria used to consider a positive response: The test item was considered as a skin sensitizer when the Similation Indice for a dose group is >= 3. Other relevant criteria such as cellularity, radioactivity levels and ear thickness were also taken into account for the interpretation of results.
TREATMENT PREPARATION AND ADMINISTRATION:
RANGE FINDING TESTS:
- Compound solubility: Due to the unsatisfactory solubility of the test item in the first recommended vehicle (acetone/olive oil (4/1, (v/v)),
dimethylformamide was chosen from the other proposed vehicles. A solution was obtained at the maximum tested concentration of 50%.
- Irritation: Measurement of the ear thickness (using a micrometer) was performed each day before treatment and 72 hours after the last application. The test item was non-irritant in the preliminary test, whatever the concentration. The highest concentration retained for the main test was therefore the maximal practicable concentration (100%), according to the criteria specified in the International Guidelines.
- Lymph node proliferation response: no measurement
TREATMENT PREPARATION AND ADMINISTRATION:
TREATMENT PREPARATION
The concentrations were expressed in % (v/v). The test item was prepared at the chosen concentrations in AOO by successive dilutions. The dosage form preparations were homogenized by vortex. The reference item was dissolved in AOO at the concentration of 25% (v/v). All dosage form preparations were made freshly on the morning of administration and any unused material was discarded that same day.
TREATMENT ADMINISTRATION:
On days 1, 2 and 3, a dose-volume of 25 µL of the control or dosage form preparations was applied to the dorsal surface of both ears, using an adjustable pipette fitted with a plastic tip. In order to avoid licking and to ensure an optimized application of the test materials, the animals were placed under light isoflurane anesthezia during the administration. No massage was performed but the tip was used to spread the preparation over the application sites. No rinsing was performed between each application.
After 2 days of resting, the proliferation of lymphocytes in the lymph node draining the application site was measured by incorporation of tritiated methyl thymidine (day 6). The obtained values were used to calculate Simulation Indices (SI). - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- No data
Results and discussion
- Positive control results:
- In the positive control group given HCA at the concentration of 25%, a moderate increase in cellularity and a stimulation index exceeding the threshold value of 3 (SI = 11.77) were noted. The study was therefore considered valid. See Table 7.4.1/1
In vivo (LLNA)
Resultsopen allclose all
- Parameter:
- SI
- Value:
- 0.79
- Test group / Remarks:
- concentration: 5% , 4 animals
- Parameter:
- SI
- Value:
- 1.13
- Test group / Remarks:
- Concentration 10%, 4 animals
- Parameter:
- SI
- Value:
- 0.91
- Test group / Remarks:
- Concentration 25%, 4 animals
- Parameter:
- SI
- Value:
- 0.67
- Test group / Remarks:
- Concentration 50%, 4 animals
- Parameter:
- SI
- Value:
- 1.13
- Test group / Remarks:
- concentration 100%, 4 animals
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: See Table 7.4.1/1
Any other information on results incl. tables
Table 7.4.1/1: Results of the main test
Treatment and Concentration |
Cell count |
Viability % |
Amounts of cells (x106cells) |
Cellularity index |
N° of nodes per group |
Dpm per group |
Dpm per node |
SI |
Increase ear thickness (% between day 1 and 6) |
Irritation level |
EC3value |
|
Viable |
Dead |
|||||||||||
Vehicle |
63 |
2 |
96.92 |
6.30 |
|
8 |
946.08 |
118.26 |
|
2.06 |
|
NA |
Test item 5% |
77 |
7 |
91.67 |
7.70 |
1.22 |
8 |
744.46 |
93.06 |
0.79 |
4.08 |
I |
|
Test item 10% |
250 |
14 |
94.70 |
25.00 |
3.97 |
8 |
1073.39 |
134.17 |
1.13 |
6.06 |
I |
|
Test item 25% |
201 |
4 |
98.05 |
20.10 |
3.19 |
8 |
862.99 |
107.87 |
0.91 |
5.15 |
I |
|
Test item 50% |
81 |
14 |
85.26 |
8.10 |
1.29 |
8 |
634.73 |
79.34 |
0.67 |
0.00 |
I |
|
Test item 100% |
105 |
15 |
87.50 |
10.50 |
1.67 |
6 |
1066.25 |
133.28 |
1.13 |
1.01 |
I |
|
HCA 25% |
248 |
21 |
92.19 |
49.60 |
7.87 |
8 |
11136.93 |
1392.12 |
11.77 |
|
|
SI = simulation index = dpm of treated group / dpm of control group
dpm = disintegration per minute
I = non-irritant (increase in ear thickness < 10 %)
EC value = theoretical concentration resulting in a SI value of 3
NA = Not applicable
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the experimental conditions of this study, Methyl-2-glutaronitrile did not induce delayed contact hypersensitivity in the murine Local Lymph Node Assay.
- Executive summary:
In a dermal sensitization study performed according to the OECD test guideline No. 429 and in compliance with Good Laboratory Practice,
2 -methylglutaronitrile (purity: 88.4%) was tested in female CBA/J mice using the Local Lymph Node Assay.
A preliminary test was first performed in order to define the concentrations of test item to be used in the main test. In the main test, 28 female CBA/J mice were allocated to seven groups:
· five treated groups of four animals receiving the test item Methyl-2-glutaronitrile at the concentration of 5, 10, 25, 50 or 100% in dimethylformamide (vehicle),
· one negative control group of four animals receiving the vehicle,
· one positive control group of four animals receiving the reference item, a-hexylcinnamaldehyde (HCA), a moderate sensitizer, at the concentration of 25% in a mixture acetone/olive oil (4/1; v/v).
During the induction phase, the test item, vehicle or reference item was applied over the ears (25 µL per ear) for 3 consecutive days (days 1, 2 and 3). After 2 days of resting, the proliferation of lymphocytes in the lymph node draining the application site was measured by incorporation of tritiated methyl thymidine (day 6). The obtained values were used to calculate stimulation indices (SI).
The irritant potential of the test item was assessed in parallel by measurement of ear thickness on days 1, 2, 3 and 6.
Due to the unsatisfactory solubility of the test item in the first recommended vehicle (acetone/olive oil (4/1, v/v)), dimethylformamide was chosen from the other proposed vehicles. A solution was obtained at the maximum tested concentration of 50%.
Consequently, the concentrations selected for the preliminary test were 10, 25, 50 and 100%. Since the test item was non-irritant in the preliminary test, the highest concentration retained for the main test was the maximal practicable concentration (100%).
No mortality related to treatment and no clinical signs were observed during the study.
No cutaneous reactions and no notable increase in ear thickness were observed in the animals of the treated groups.
A significant lymphoproliferation was noted in the positive control group given HCA at 25%, the study was therefore considered valid. No lymphoproliferation was noted at any tested concentration of 2 -methylglutaronitrile.
Under the experimental conditions of this study, 2 -methylglutaronitrile is considered as not sensitizer. Therefore, no classification is required according to the CLP regulation (1272/2008) and to the Directive 67/548/CEE.
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