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EC number: 211-892-8 | CAS number: 706-14-9
- 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 irritation / corrosion
Administrative data
- Endpoint:
- skin irritation / corrosion
- Remarks:
- other: In vitro study regulatory validated
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- From March 13 to April 06, 2012
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: OECD guideline study: GLP. γ-Nonalactone, as aliphatic γ-lactone, is considered adequate for read-across purpose (see §7.1 "Toxicokinetics").
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
- Report date:
- 2012
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- Deviations:
- yes
- Remarks:
- IL-1α assay was added to the standard protocol
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Inspected on 22-23 November 2011
Test material
- Reference substance name:
- Nonan-4-olide
- EC Number:
- 203-219-1
- EC Name:
- Nonan-4-olide
- Cas Number:
- 104-61-0
- Molecular formula:
- C9H16O2
- IUPAC Name:
- 5-pentyldihydrofuran-2(3H)-one
- Test material form:
- liquid
- Details on test material:
- - Name of test material (as cited in study report): gamma-Nonalactone
- Physical state: clear colourless to pale yellow liquid
Constituent 1
Test animals
- Species:
- human
- Details on test animals or test system and environmental conditions:
- Three-dimensional human epidermis model ("small" size of 0.38 cm²), supplied by SKINETHIC Laboratories, Lyon, France constituted by:
- a collagen type I matrix, coated with type IV collagen
- a differentiated and stratified epidermis model from human keratinocytes, obtained after 13-day culture period.
All biological components of the epidermis and the kit culture medium have been tested for the absence of viruses, bacteria and mycoplasma.
The quality was assessed by an MTT cytotoxicity test and by histological examination (by SKINETHIC).
Epidermis was treated at D15.
Test system
- Type of coverage:
- open
- Vehicle:
- unchanged (no vehicle)
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied: 10 µL - Duration of treatment / exposure:
- 15 ± 0.5 min
- Number of animals:
- 3 epidermis/product
- Details on study design:
- Before the beginning of the study, the non-specific MTT reduction by the test item was checked by incubating MTT solution and 10 µL test item for 3 hours ± 30 minutes and checking the colour of the solution. The staining power of the test item was checked afer the addition of mineral oil to 10 µL test item and agitation 15 ± 0.5 minutes at room temperature
Application of the test item and control:
- negative control: 10 µL of PBS+ to each epidermis surface
- positive control: 10 µL of SDS solution at 5% (w/v) in distilled water; after 7 minutes contact time, an intermediate re-spreading is done
- test substance: 10 µL of the test item, as supplied
- contact timepoint for all products: 15 ± 0.5 minutes at room temperature
Rinsing:
- epidermis rinsed thoroughly with 25 mL of PBS+
- remaining product removed with a cotton-bud
Incubation:
Plates incubated during 42 ± 1 hours in CO2 incubator with maintenance medium
Medium sampling for IL-1α dosage:
- at the end of the 42 hours incubation period, shake the plates during 15 ± 2 minutes to homogenize the released mediators in the medium
- transfer 1.6 mL of each incubation medium in microtubes
- after realisation of the trial, measurement at 450 nm
MTT colouring:
- epidermis incubated for 3 hours ± 5 minutes in MTT solution in the CO2 incubator
Formazan extraction
- in 500 µL of acidic isopropanol stored at 4 hours ± 30 minutes at room temperature, protected from light or during 70 ± 5 hours at 4 °C
- measurement of OD at 570 nm
Results and discussion
In vivo
Results
- Irritation parameter:
- other: Viability % (MTT assay)
- Basis:
- mean
- Time point:
- other: 15 min
- Score:
- 74.6
- Remarks on result:
- other: ± 2.8
- Irritant / corrosive response data:
- Negative control (PBS+): mean O.D. = 0.924
Positive control (SDS): Viability = 15.2 ± 2.0 % - Other effects:
- None
Any other information on results incl. tables
Table 7.3.1: MTT conversion assay
|
|
OD1 |
OD2 |
Mean |
SD |
Viability % |
Mean viability % |
SD |
Negative control |
Epidermis 1 |
0.808 |
0.893 |
0.851 |
0.060 |
92.1 |
100 |
7.5 |
Epidermis 2 |
0.956 |
1.019 |
0.988 |
0.045 |
106.9 |
|||
Epidermis 3 |
0.912 |
0.953 |
0.933 |
0.029 |
101.0 |
|||
Mean |
/ |
/ |
0.924 |
/ |
/ |
|||
Positive control |
Epidermis 1 |
0.156 |
0.167 |
0.162 |
0.008 |
17.5 |
15.2 |
2.0 |
Epidermis 2 |
0.129 |
0.121 |
0.125 |
0.006 |
13.5 |
|||
Epidermis 3 |
0.130 |
0.140 |
0.135 |
0.007 |
14.6 |
|||
Gamma- Nonalactone |
Epidermis 1 |
0.668 |
0.667 |
0.668 |
0.001 |
72.3 |
74.6 |
2.8 |
Epidermis 2 |
0.670 |
0.694 |
0.682 |
0.017 |
73.8 |
|||
Epidermis 3 |
0.708 |
0.729 |
0.719 |
0.015 |
77.8 |
INTERLEUKINE 1 ALPHA (IL-1α) ASSAY:
|
O.D. |
Concentration |
Mean concentration |
Standard deviation |
Final conc |
||||
|
Epidermis 1 |
Epidermis 2 |
Epidermis 3 |
Epidermis 1 |
Epidermis 2 |
Epidermis 3 |
|||
Negative control |
0.020 |
0.031 |
0.046 |
-5.8 |
-4.3 |
-2.2 |
-4.1 |
1.81 |
/ |
Positive control |
1.609 |
1.737 |
1.683 |
214.9 |
232.6 |
225.1 |
224.2 |
8.92 |
228.3 |
Gamma-Nonalactone |
0.802 |
0.749 |
0.767 |
102.8 |
95.4 |
97.9 |
98.7 |
3.74 |
102.8 |
Although IL-1 alpha proved to be useful to acquire additional information on the irritant potential of chemicals, only results from the MTT assay are currently used for classification and labelling according to the EU classification system. With a IL-1α concentration higher than 60 pg/mL, it could be considered that Gamma Nonalactone may have a skin irritant potential.
Applicant's summary and conclusion
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Under the test conditions, Gamma-Nonalactone is not classified as irritating to skin according to the criteria of Annex VI of the Directive 67/548/EEC and the Annex I of the Regulation (EC) No (1272/2008 (CLP).
- Executive summary:
The purpose of this test was to evaluate the skin irritation potential of the Gamma-Nonalactone using the EPISKIN® reconstructed human epidermis model. The principle of the assay was based on the measurement of cytotoxicity in reconstructed human epidermal cultures following topical exposure to the test item by means of the colourimetric MTT reduction assay. Cell viability is measured by enzymatic reduction of the yellow MTT tetrazolium salt (3‑[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) to a blue formazan salt (within the mitochondria of viable cells) in the test item treated tissues relative to the negative controls. This method was designed to be compatible with the following:
- OECD Guidelines for the Testing of Chemicals No. 439 “In Vitro Skin Irritation” (adopted 22 July 2010)
- Method B.46 of Commission Regulation (EC) No. 440/2008/EC
Triplicate tissues were treated with Gamma-Nonalactone for an exposure period of 15 minutes. At the end of the exposure period each tissue was rinsed before incubating for 42 hours. At the end of the post‑exposure incubation period each tissue was taken for MTT-loading. After MTT loading a total biopsy of each epidermis was made and placed into micro tubes containing acidified isopropanol for extraction of formazan crystals out of the MTT‑loaded tissues.
At the end of the formazan extraction period each tube was mixed thoroughly and duplicate 200 µl samples were transferred to the appropriate wells of a pre-labelled 96-well plate. The optical density was measured at 540 nm.
Data are presented in the form of percentage viability (MTT reduction in the test item treated tissues relative to negative control tissues).
The relative mean viability of the test item treated tissues was74.6 ± 2.8 % after the 15‑Minute exposure period.
The quality criteria required for acceptance of results in the test were satisfied.
γ-Nonalactone was not considered as irritant according to the Directive 67/548/EEC and the Regulation (EC) No. 1272/2008 (CLP).
γ-Nonalactone, as aliphatic γ-lactone, is considered adequate for read-across purpose (see §7.1 "Toxicokinetics").
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