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EC number: 203-219-1 | CAS number: 104-61-0
- 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 17 July – 17 October 2008
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP study conducted according to OECD Guideline 474 with minor deviations: relative humidity in the animal rooms ranged between 30 – 114 % instead of 30–70 %; body weight of the animals were not reported
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:
- 2 009
- Report date:
- 2009
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- yes
- Remarks:
- relative humidity in the animal rooms ranged between 30 – 114 % instead of 30–70 %; body weight of the animals were not reported
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- micronucleus assay
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-pentyloxolan-2-one
- Details on test material:
- - Name of test material (as cited in study report): γ-nonalactone (Aldehyde C-18) FFC
- Analytical purity: 99.0 % (GLC)
- Purity test date: 04 March 2009
- Batch No.: 2007302-0001
- Expiration date of the batch: 29 October 2012
- Storage condition of test material: At room temperature under nitrogen
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Laboratories GmbH, Borchen, Germany
- Age at start of acclimatization: 6 - 8 weeks
- Weight at study initiation: Male: 36.5 ± 1.8 g; female: 27.3 ± 2.0 g
- Housing: Animals were housed individually in Makrolon Type I cages, with wire mesh top
- Diet: Pelleted standard diet (Harlan Laboratories GmbH, Borchen, Germany), ad libitum
- Water: Tap water (Gemeindewerke, Rossdorf, Germany), ad libitum
- Acclimation period: Minimum 5 days
ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30-114 %
- Photoperiod: 12 h dark / 12 h artificial light
Administration / exposure
- Route of administration:
- oral: unspecified
- Vehicle:
- - Vehicle(s)/solvent(s) used: Corn oil
- Source: Sigma-Aldrich Vertriebs GmbH, Deisenhofen, Germany
- Justification for choice of solvent/vehicle: Nontoxic to animals
- Amount of vehicle: 10 mL/kg bw - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: On the day of the experiment, the test item was formulated in corn oil.
- Duration of treatment / exposure:
- 24 h (in all test groups) and 48 h (in 2000 mg/kg bw group)
- Frequency of treatment:
- Once
- Post exposure period:
- Not applicable
Doses / concentrations
- Remarks:
- Doses / Concentrations:
500, 1000 and 2000 mg/kg bw
Basis:
actual ingested
- No. of animals per sex per dose:
- - Pre-experiment 1 and 2: 2/sex/dose
- Main experiment: 6/sex/dose - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide
- Source: Sigma-Aldrich Vertriebs GmbH, Deisenhofen, Germany
- Solvent: Deionised water
- Route of administration: Oral
- Doses: 40 mg/kg bw
- Volume administered: 10 mL/kg bw
Examinations
- Tissues and cell types examined:
- - Femora bones were removed for marrow extraction and the prepared slides were examined for polychromatic erythrocytes (PCEs), normochromatic erythrocytes (NCEs) and total erythrocytes.
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: Dose selection was based on the results of preliminary range-finding tests conducted on 2 mice/sex/dose at 1000 and 2000 mg/kg bw. No significant toxic signs were recorded.
TREATMENT AND SAMPLING TIMES:
- At 24 and 48 h after exposure, animals were sacrificed using CO2 followed by bleeding.
- Femora were removed, the epiphyses were cut off and the marrow was flushed out with fetal calf serum using a syringe.
- Cell suspension was centrifuged at 1500 rpm for 10 minutes and the supernatant was discarded.
DETAILS OF SLIDE PREPARATION:
- A small drop of the re-suspended cell pellet was spread on a slide.
- Smear was air-dried and then stained with May-Grünwald /Giemsa stain.
METHOD OF ANALYSIS:
- Evaluation of the slides was performed using NIKON microscopes with 100x oil immersion objectives.
- At least 2000 polychromatic erythrocytes (PCE) were analysed per animal for micronuclei.
- To describe a cytotoxic effect the ratio between polychromatic and normochromatic erythrocytes was determined in the same sample and expressed in polychromatic erythrocytes per 2000 erythrocytes.
- Ten animals (5 males, 5 females) per test group were evaluated. - Evaluation criteria:
- - A test item is classified as mutagenic if it induces either a dose-related increase or a clear increase in the number of micronucleated polychromatic erythrocytes in a single dose group. Statistical methods (nonparametric Mann-Whitney test) were used as an aid in evaluating the results. However, the primary point of consideration is the biological relevance of the results.
- A test item that fails to produce a biological relevant increase in the number of micronucleated polychromatic erythrocytes is considered non-mutagenic in this system. - Statistics:
- Statistical significance at 5 % level (p < 0.05) was evaluated by non-parametric Mann-Whitney test.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF PRE-EXPERIMENT
- Dose range: 1000 mg/kg bw (first pre-experiment, 2/sex) and 2000 mg/kg bw (second pre-experiment, 2/sex)
- Clinical signs of toxicity in test animals: See table 7.6.2/1
RESULTS OF MAIN EXPERIMENT
- See table 7.6.2/2 for toxic reactions
- See table 7.6.2/3 for frequency of micronuclei in polychromatic erythrocytes and PCE/total erythrocytes ratio
Any other information on results incl. tables
Table 7.6.2/1: Pre-experiment - Toxic reactions
Dose levels (mg/kg bw) |
Toxic reactions |
hours post-treatment (male/female) |
|||||
1 h |
2-4 h |
6 h |
24 h |
30 h |
48 h |
||
Pre-experiment 1 |
|||||||
1000 |
Reduction of spontaneous activity |
0/2 |
0/0 |
0/0 |
0/0 |
-/- |
0/0 |
Ruffled fur |
2/2 |
2/2 |
2/2 |
2/2 |
-/- |
0/0 |
|
Pre-experiment 2 |
|||||||
2000 |
Reduction of spontaneous activity |
2/2 |
2/2 |
2/2 |
0/0 |
0/0 |
0/0 |
Abdominal position |
2/2 |
0/0 |
0/0 |
0/0 |
0/0 |
0/0 |
|
Ruffled fur |
2/2 |
2/2 |
2/2 |
2/2 |
2/2 |
2/2 |
|
Apathy |
2/2 |
1/2 |
0/0 |
0/0 |
0/0 |
0/0 |
-/- no observation was made
Table 7.6.2/2: Main experiment - Toxic reactions
Dose levels (mg/kg bw) |
No. of animals per sex |
hours post-treatment (male/female) |
Toxic reactions |
||||
Ruffled fur |
Reduction of spontaneous activity |
Abdominal position |
Tumbling |
Apathy |
|||
500 |
6 |
1 h |
2/1 |
- |
- |
- |
- |
2-4 h |
6/2 |
- |
- |
- |
- |
||
6 h |
6/3 |
- |
- |
- |
- |
||
24 h |
0/0 |
- |
- |
- |
- |
||
1000 |
6 |
1 h |
6/6 |
4/0 |
- |
- |
- |
2-4 h |
6/6 |
4/0 |
- |
- |
- |
||
6 h |
6/6 |
3/1 |
- |
- |
- |
||
24 h |
6/6 |
0/0 |
- |
- |
- |
||
2000 |
12 |
1 h |
12/12 |
12/12 |
4/3 |
7/5 |
4/6 |
2-4 h |
12/12 |
12/12 |
0/0 |
0/0 |
0/0 |
||
6 h |
12/12 |
12/12 |
0/0 |
0/0 |
0/0 |
||
24 h |
12/12 |
0/0 |
0/0 |
0/0 |
0/0 |
||
48 h* |
3/4 |
0/0 |
0/0 |
0/0 |
0/0 |
*: data only from 6 animals per sex.
Table 7.6.2/3: Results of micronucleus test
Test group |
Dose mg/kg bw |
Sampling time (h) |
PCEs with micronuclei (%) |
Range |
PCE per 2000 erythrocytes |
Vehicle |
0 |
24 |
0.120 |
0 - 6 |
1159 |
Gamma-nonalactone |
500 |
24 |
0.140 |
1 - 5 |
1195 |
1000 |
24 |
0.105 |
0 - 6 |
1169 |
|
2000 |
24 |
0.115 |
0 - 8 |
1178 |
|
2000 |
48 |
0.160 |
1 - 6 |
1088 |
|
Positive control |
40 |
24 |
2.505* |
13 - 90 |
1132 |
*: p<0.0001
Results of formulation analysis:
- Representative analytical samples of the application formulations were collected and analysed by GC coupled to FID detector.
- The identity of the test material was confirmed by its retention time which was similar to that measured in the working standards and the test item content in all samples was found to be within the accepted range of ±20 % of the nominal content.Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
Under the test conditions, γ-nonalactone is not considered as clastogenic in the mouse bone marrow micronucleus assay according to the Directive 67/548/EEC and the Regulation (EC) No. 1272/2008 (CLP). - Executive summary:
In an in vivo bone marrow micronucleus assay, performed according to OECD Guideline 474 and in compliance with GLP, groups of NMRI mice (6/sex/dose) were given a single oral dose of γ-nonalactone in corn oil at concentrations of 0, 500, 1000 and 2000 mg/kg bw. Positive control group was treated with cyclophosphamide at 40 mg/kg bw. Bone marrow of 5 mice/sex/dose was extracted after 24 hours (in all test groups) or 48 hours (in 2000 mg/kg bw group) of exposure and the prepared slides were scanned to determine the frequency of micronuclei in 2000 polychromatic erythrocytes (PCEs) per animal. In addition, PCE:NCE ratio was determined in the same sample and expressed as PCE/2000 erythrocytes. A preliminary range-finding test was also conducted on 2 mice/sex/dose at 1000 and 2000 mg/kg bw in which no toxic sign was recorded.
No statistically significant increases in the frequency of micronucleated PCEs were observed at any dose levels. In comparison to the corresponding vehicle controls there was no biologically relevant or statistically significant enhancement in the frequency of the detected micronuclei at any preparation interval after administration of the test item and with any dose level used. Positive control induced the appropriate response.
Under the test conditions, γ-nonalactone is not considered as clastogenic in the mouse bone marrow micronucleus assay according to the Directive 67/548/EEC and of the Regulation (EC) No. 1272 /2008 (CLP).
This study is considered as acceptable and satisfies the requirement for a micronucleus assay.
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