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EC number: 419-050-3 | CAS number: 79944-37-9 AMINODIOXEPAN
- 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
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- May 1993 to July 1993
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 993
- Report date:
- 1993
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- 26 May 1983
- GLP compliance:
- yes
- Type of assay:
- mammalian erythrocyte micronucleus test
Test material
- Reference substance name:
- trans-(5RS,6SR)-6-amino-2,2-dimethyl-1,3-dioxepan-5-ol
- EC Number:
- 419-050-3
- EC Name:
- trans-(5RS,6SR)-6-amino-2,2-dimethyl-1,3-dioxepan-5-ol
- Cas Number:
- 79944-37-9
- Molecular formula:
- C7H15NO3
- IUPAC Name:
- 6-amino-2,2-dimethyl-1,3-dioxepan-5-ol
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Details on species / strain selection:
- The mouse was chosen as test animal since a wide range of experience with regard to micronucleus tests exists and since the mouse has been recommended by national and international authorities.
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzheim, FRG
- Age at study initiation: adult, 8-9 weeks
- Weight at study initiation: 25-35 and 25-29 g for males and females, respectively
- Fasting period before study: 17-21 h
- Housing: housed individually in Macrolon type ll cages containing wood-chip bedding.
- Diet (e.g. ad libitum): ad libitum, (Altromin®R; Altromin, Lage, FRG)
- Water (e.g. ad libitum): ad libitum, mildly acidified demineralized water
- Acclimation period: 8 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23
- Humidity (%): 46-50
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- - Vehicle(s)/solvent(s) used:physiological saline
- Concentration of test material in vehicle: 50, 100 and 200 mg/mL - Duration of treatment / exposure:
- treated once and killed after 24 and 48 h
- Frequency of treatment:
- once
Doses / concentrationsopen allclose all
- Dose / conc.:
- 2 000 mg/kg bw (total dose)
- Dose / conc.:
- 1 000 mg/kg bw (total dose)
- Dose / conc.:
- 500 mg/kg bw (total dose)
- No. of animals per sex per dose:
- 10-13 per treatement and 10 in the negative control group and 5 in the positive control group
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide
- Justification for choice of positive control(s): Cyclophosphamide, a known mutagen, was used as a positive control.
- Route of administration: intraperitoneal
- Doses / concentrations: 30 mg/kg bw
Examinations
- Tissues and cell types examined:
- bone marrow from femurs
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: lt was assumed from an acute toxicity study in male mice that 2 g/kg would be a dose level at which toxic effects might be noted (at 2g/kg all animals showed moderate apathy).
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):
5 males and 5 females from each of the negative control and the treatment groups were killed by carbon dioxide asphyxiation ca. 24 or 48 hours after treatment (the positive control animals were killed 24 hours after treatment) and both femurs were dissected out from each animal.
DETAILS OF SLIDE PREPARATION:
The bone marrow was flushed/aspirated into fetal calf serum. The resulting cell suspensions were centrifuged and smears were prepared from drops of the cell pellets which had been resuspended in a few drops of serum. The slides were air-dried and stained using May-Gruenwald and Giemsa solutions.
METHOD OF ANALYSIS:
The slides were coded and analysed "blind" in random order. The stained smears were examined using oil immersion high power magnification in regions where cells were well-spread and stained. The slides were examined for the incidence of micronucleated cells per 2000 polychromatic (POE) and 1000 normochromatic (NCE) erythrocytes per animal. The ratio of polychromatic to normochromatic erythrocytes was calculated on the basis of 1000 NCE scored.
- Statistics:
- The statistical analysis was conducted for each of the following variables:
p1: proportion of micronucleated PCE
p2: proportion of micronucleated NOE
p3: ratio of PCE/NCE
For investigation of treatment differences the variables p1 and p2- were arc sin transformed. The analyses were conducted separately for the sample times. Regarding the first sample time one-sided t-tests were performed to assess the difference between positive and negative controls with pooled values for both sexes; the positive control group was then excluded from further analysis. Thereafter in a two-factorial ANOVA (factors "sex", treatment") for each sample time it was investigated as to whether any treatment effect was present. In case of significant interactions, comparisons between the control and each of the treatment groups were conducted separately for each sex. Where no significant interactions occurred but a global treatment effect, comparisons were performed with values pooled for both sexes. The pair-wise comparisons were performed with one-sided t-tests (increase of p1 and D2, decrease of p3), using the error estimate of the ANOVA table. The test levels were always or = 0.05 (least significant differences test-LSD). In addition to the non-transformed individual data the arithmetic means and standard deviations were included.
Results and discussion
Test results
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- in the high dose group
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
Any other information on results incl. tables
After application of the high dose only 1 male and 2 females out of 13 males and 13 females survived the first day. Therefore, only two dose groups could be evaluated. Signs of slight toxicity could be observed in 4 out of 10 males and 4 out of 10 females in the mid dose group.
Regarding micronucleated PCE and NCE counts as well as the ratio POE/NCE, there were no biologically relevant or statistically significant differences (p > 0.05) at any sample time. The positive control group showed a significant increase in micronucleated POE and NCE counts (p < 0.05).
MICRONUCLEUS ASSAY RESULTS
MICRONUCLEI (IN PER MILL) SCORED PER TWO THOUSAND POLYCHROMATIC AND ONE THOUSAND ERYTHROCYTES WITH RATIO PCE/NCE
Negative Control 10 mL/kg bw | |||||||
24 h post application | 48 h post application | ||||||
No. | PCE (M) | NCE (M) | Ratio PCE/NCE | No. | PCE (M) | NCE (M) | Ratio PCE/NCE |
Male | Male | ||||||
1 | 1.00 | 1.00 | 0.97 | 6 | 1.00 | 1.00 | 0.92 |
2 | 0.50 | 1.00 | 0.96 | 7 | 0.00 | 1.00 | 1.14 |
3 | 1.00 | 1.00 | 0.96 | 8 | 1.00 | 1.00 | 1.12 |
4 | 0.50 | 0.00 | 0.98 | 9 | 1.50 | 1.00 | 1.02 |
5 | 1.50 | 1.00 | 0.90 | 10 | 1.50 | 1.00 | 1.11 |
MV= | 0.90 | 0.80 | 0.95 | MV= | 1.00 | 1.00 | 1.06 |
SD= | 0.42 | 0.45 | 0.03 | SD= | 0.61 | 0.00 | 0.09 |
N= | 5 | 5 | 5 | N= | 5 | 5 | 5 |
Female | Female | ||||||
1 | 0.50 | 0.00 | 0.95 | 6 | 1.00 | 2.00 | 0.94 |
2 | 1.00 | 1.00 | 1.05 | 7 | 0.50 | 0.00 | 1.02 |
3 | 1.00 | 1.00 | 0.87 | 8 | 0.50 | 1.00 | 1.06 |
4 | 0.50 | 0.00 | 0.95 | 9 | 1.00 | 1.00 | 1.01 |
5 | 0.50 | 1.00 | 1.10 | 10 | 1.00 | 0.00 | 0.88 |
MV= | 0.70 | 0.60 | 0.98 | MV= | 0.80 | 0.80 | 0.98 |
SD= | 0.27 | 0.55 | 0.09 | SD= | 0.27 | 0.84 | 0.07 |
N= | 5 | 5 | 5 | N= | 5 | 5 | 5 |
Male + Female | Male + Female | ||||||
MV= | 0.80 | 0.70 | 0.97 | MV= | 0.90 | 0.90 | 1.02 |
SD= | 0.35 | 0.48 | 0.07 | SD= | 0.46 | 0.57 | 0.09 |
N= | 10 | 10 | 10 | N= | 10 | 10 | 10 |
0.5 g/kg bw | |||||||
24 h post application | 48 h post application | ||||||
No. | PCE (M) | NCE (M) | Ratio PCE/NCE | No. | PCE (M) | NCE (M) | Ratio PCE/NCE |
Male | Male | ||||||
1 | 1.00 | 2.00 | 0.96 | 6 | 1.00 | 1.00 | 1.07 |
2 | 0.50 | 0.00 | 0.96 | 7 | 0.50 | 1.00 | 1.06 |
3 | 0.50 | 0.00 | 1.15 | 8 | 0.50 | 0.00 | 1.14 |
4 | 1.00 | 1.00 | 1.00 | 9 | 1.00 | 1.00 | 1.04 |
5 | 1.50 | 1.00 | 1.09 | 10 | 1.00 | 0.00 | 0.92 |
MV= | 0.90 | 0.80 | 1.03 | MV= | 0.80 | 0.60 | 1.05 |
SD= | 0.42 | 0.84 | 0.08 | SD= | 0.27 | 0.55 | 0.08 |
N= | 5 | 5 | 5 | N= | 5 | 5 | 5 |
Female | Female | ||||||
1 | 0.50 | 2.00 | 0.98 | 6 | 1.00 | 1.00 | 1.10 |
2 | 1.00 | 0.00 | 1.00 | 7 | 0.50 | 0.00 | 0.91 |
3 | 0.50 | 1.00 | 0.94 | 8 | 0.50 | 1.00 | 1.06 |
4 | 1.00 | 1.00 | 0.96 | 9 | 0.50 | 1.00 | 0.94 |
5 | 0.50 | 0.00 | 0.90 | 10 | 0.50 | 1.00 | 1.13 |
MV= | 0.70 | 0.80 | 0.96 | MV= | 0.60 | 0.80 | 1.03 |
SD= | 0.27 | 0.84 | 0.04 | SD= | 0.22 | 0.45 | 0.10 |
N= | 5 | 5 | 5 | N= | 5 | 5 | 5 |
Male + Female | Male + Female | ||||||
MV= | 0.80 | 0.80 | 0.99 | MV= | 0.70 | 0.70 | 1.04 |
SD= | 0.35 | 0.79 | 0.07 | SD= | 0.26 | 0.48 | 0.09 |
N= | 10 | 10 | 10 | N= | 10 | 10 | 10 |
1.0 g/kg bw | |||||||
24 h post application | 48 h post application | ||||||
No. | PCE (M) | NCE (M) | Ratio PCE/NCE | No. | PCE (M) | NCE (M) | Ratio PCE/NCE |
Male | Male | ||||||
1 | 1.00 | 0.00 | 0.96 | 6 | 1.00 | 1.00 | 1.10 |
2 | 1.00 | 1.00 | 1.03 | 7 | 0.50 | 1.00 | 1.04 |
3 | 1.00 | 1.00 | 1.06 | 8 | 0.50 | 0.00 | 0.97 |
4 | 1.00 | 0.00 | 0.95 | 9 | 1.00 | 1.00 | 0.99 |
5 | 1.00 | 1.00 | 0.83 | 10 | 1.00 | 0.00 | 0.92 |
MV= | 1.00 | 0.60 | 0.96 | MV= | 0.80 | 0.60 | 1.00 |
SD= | 0.00 | 0.55 | 0.09 | SD= | 0.27 | 0.55 | 0.07 |
N= | 5 | 5 | 5 | N= | 5 | 5 | 5 |
Female | Female | ||||||
1 | 0.50 | 0.00 | 1.00 | 6 | 1.00 | 2.00 | 1.06 |
2 | 0.50 | 1.00 | 1.05 | 7 | 0.50 | 1.00 | 1.10 |
3 | 0.50 | 1.00 | 1.03 | 8 | 1.00 | 1.00 | 1.05 |
4 | 1.00 | 1.00 | 0.90 | 9 | 0.50 | 0.00 | 1.07 |
5 | 0.50 | 1.00 | 1.01 | 10 | 0.50 | 0.00 | 1.07 |
MV= | 0.60 | 0.80 | 1.00 | MV= | 0.70 | 0.80 | 1.07 |
SD= | 0.22 | 0.45 | 0.06 | SD= | 0.27 | 0.84 | 0.02 |
N= | 5 | 5 | 5 | N= | 5 | 5 | 5 |
Male + Female | Male + Female | ||||||
MV= | 0.80 | 0.70 | 0.98 | MV= | 0.75 | 0.70 | 1.04 |
SD= | 0.26 | 0.48 | 0.07 | SD= | 0.26 | 0.67 | 0.06 |
N= | 10 | 10 | 10 | N= | 10 | 10 | 10 |
Cyclophosphamide 30 mg /kg bw | |||||||
24 h post application |
| ||||||
No. | PCE (M) | NCE (M) | Ratio PCE/NCE | ||||
Male | |||||||
1 | 9.50 | 2.00 | 0.95 | ||||
2 | 11.00 | 1.00 | 0.95 | ||||
3 | 13.50 | 2.00 | 0.89 | ||||
4 | 15.00 | 1.00 | 1.00 | ||||
5 | 15.00 | 1.00 | 0.96 | ||||
MV= | 12.80 | 1.40 | 0.95 | ||||
SD= | 2.46 | 0.55 | 0.04 | ||||
N= | 5 | 5 | 5 | ||||
Female | |||||||
1 | 10.00 | 2.00 | 0.98 | ||||
2 | 7.50 | 1.00 | 0.89 | ||||
3 | 10.50 | 3.00 | 0.87 | ||||
4 | 11.00 | 1.00 | 0.81 | ||||
5 | 9.50 | 1.00 | 0.96 | ||||
MV= | 9.70 | 1.60 | 0.90 | ||||
SD= | 1.35 | 0.89 | 0.07 | ||||
N= | 5 | 5 | 5 | ||||
Male + Female | |||||||
MV= |
|
|
| ||||
SD= |
|
|
| ||||
N= | 10 | 10 | 10 | ||||
PCB = POLYCHROMATIC ERYTHROCYTES NCE = NORMOCHROMATIC ERYTHROCYTES PCE(M) = MICRONUCLEATED POLYCHROMATIC ERYTHROCYTES (IN PER MILL) NCE(H) = MICRONUCLEATED NORMOCHROMATIC ERYTHROCYTES (IN PER HILL) MV: MEAN VALUE SD: STANDARD DEVIATION N: NUMBER 0F ANIMALS PER GROUP
|
Applicant's summary and conclusion
- Conclusions:
- Evaluation of the data showed that Aminodioxepan has no evidence of mutagenic potential, when administered intraperitoneally up to the toxic dose level of 1.0 g/kg in the mouse micronucleus test.
- Executive summary:
In a NMRI mouse bone marrow micronucleus assay equivalent to OECD test guideline 474, (5 animals/sex/dose) were treated intraperitoneally with Aminodioxepan (100 % a.i.) at doses of 0, 500, 1000 and 2000 mg/kg bw. Bone marrow cells were harvested at 24 and 48 h post-treatment. The vehicle was physiological saline.
There were signs of toxicity present during the study. After application of the high dose only 1 male and 2 females out of 13 males and 13 females survived the first day. Therefore, only two dose groups could be evaluated. Signs of slight toxicity could be observed in 4 out of 10 males and 4 out of 10 females in the mid dose group.
Regarding micronucleated PCE and NCE counts as well as the ratio POE/NCE, there were no biologically relevant or statistically significant differences (p > 0.05) at any sample time. The positive control group showed a significant increase in micronucleated POE and NCE counts (p < 0.05). Aminodioxepan was tested at an adequate dose (based on an acute toxicity study in mice). There was not a significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow after any treatment time.
This study is classified as acceptable. This study satisfies the requirement for Test Guideline OECD 474 for in vivo cytogenetic mutagenicity data.
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