Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 446-220-4 | CAS number: 365411-50-3
- 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:
- The experimental phases of the study were performed between 2 April 2003 and 28 May 2003.
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study conducted according to OECD TG 474 and in compliance with GLP.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 003
- Report date:
- 2003
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- -
- EC Number:
- 446-220-4
- EC Name:
- -
- Cas Number:
- 365411-50-3
- Molecular formula:
- C16 H26 O2
- IUPAC Name:
- 7,7,8,9,9-pentamethyl-2H,4H,4aH,5H,6H,7H,8H,9H,9bH-indeno[4,5-d][1,3]dioxine
- Test material form:
- other: solid
- Details on test material:
- Sponsor's identification: 2-Eyed Musk
Date received: 5 February 2003
Storage conditions: Room temperature, in the dark
For the purpose of this study the test material was freshly prepared as required as a solution at the appropriate concentration in arachis oil.
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- Sufficient albino Crl:CD-1 TM(ICR)BR strain mice were supplied by Charles River (UK) Limited, Margate, Kent. At the start of the main test the male mice weighed 24 to 29g and were approximately five to eight weeks old. After a minimum acclimatisation period of seven days the animals were selected at random and given a number unique within the study by ear punching and a number written on a colour coded cage card.
The animals were housed in groups of up to seven in solid-floor polypropylene cages with woodflake bedding. Free access to mains drinking water and food (Certified Rat and Mouse Diet 5LF2, International Product Supplies, Wellingborough, Northants, UK) was allowed throughout the study.
The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70 % respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours light and twelve hours darkness.
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- The vehicle was supplied by Analytical Supplies Limited, as follows:
Supplier's identification: Arachis oil BP
Supplier's lot number: T63
Safepharm serial number: V-2508
Date received: 16 May 2002
Description: Straw coloured, slightly viscous liquid
Storage conditions: Room temperature - Details on exposure:
- Groups, each of seven mice, were dosed once only via the intraperitoneal route with the test material at 250, 500 or 1000 mg/kg. One group of mice from each dose level was killed by cervical dislocation 24 hours following treatment and a second group dosed with 1000 mg/kg was killed after 48 hours. In addition, three further groups of mice were included in the test; two groups (seven mice) were dosed via the intraperitoneal route with the vehicle alone (arachis oil) and a third group (five mice) was dosed orally with cyclophosphamide. Cyclophosphamide is a positive control material known to produce micronuclei under the conditions of the test. The vehicle controls were killed 24 or 48 hours following dosing and positive control group animals were killed 24 hours following dosing.
All animals were observed for signs of overt toxicity and death one hour after dosing and then once daily as applicable and immediately prior to termination. - Duration of treatment / exposure:
- 24 or 48 hours.
- Frequency of treatment:
- Once only.
- Post exposure period:
- Not applicable.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
250, 500, 1000 mg/kg
Basis:
nominal conc.
- No. of animals per sex per dose:
- 7 male mice per test material dose group.
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- The positive control material was supplied by Sigma Chemicals, as follows:
Supplier's identification: Cyclophosphamide
Supplier's lot number: 91K1176
Safepharm serial number: R-2670
Date received: 5 November 2002
Storage conditions: 4°C in the dark
For the purpose of this study the positive control material was freshly prepared as required as a solution at the appropriate concentration in distilled water (IV AX batch no. A3018).
Examinations
- Tissues and cell types examined:
- Polychromatic and normochromatic erythrocytes in bone marrow.
- Details of tissue and slide preparation:
- Slide Preparation:
Immediately following termination (i.e. 24 or 48 hours following dosing), both femurs were dissected from each animal, aspirated with foetal calf serum and bone marrow smears prepared following centrifugation and re-suspension. The smears were air-dried, fixed in absolute methanol, stained in May-Griinwald/Giemsa, allowed to air-dry and coverslipped using mounting medium.
Slide Evaluation:
Stained bone marrow smears were coded and examined blind using light microscopy at x1000 magnification. The incidence of micronucleated cells per 2000 polychromatic erythrocytes (PCE-blue stained immature cells) per animal was scored. Micronuclei are normally circular in shape, although occasionally they may be oval or half-moon shaped, and have a sharp contour with even staining. In addition, the number of normochromatic erythrocytes (NCE-pink stained mature cells) associated with 1000 erythrocytes were counted; these cells were also scored for incidence of micronuclei.
The ratio of polychromatic to normochromatic erythrocytes was calculated together with appropriate group mean values and standard deviations. - Evaluation criteria:
- A comparison was made between the number of micronucleated polychromatic erythrocytes occurring in each of the test material groups and the number occurring in the corresponding vehicle control group.
A positive mutagenic response was demonstrated when a statistically significant, dose-responsive, toxicologically relevant increase in the number of micronucleated polychromatic erythrocytes was observed for either the 24 or 48-hour kill times when compared to their corresponding control group.
If these criteria were not fulfilled, then the test material was considered to be non-genotoxic under the conditions of the test.
A positive response for bone marrow toxicity was demonstrated when the dose group mean polychromatic to normochromatic ratio was shown to be statistically significantly lower than the concurrent vehicle control group. - Statistics:
- All data were statistically analysed using appropriate statistical methods as recommended by the UKEMS Sub-committee on Guidelines for Mutagenicity Testing Report, Part III (1989). The data was analysed using Student's t-test (two tailed) and any significant results were confirmed using the one way analysis of variance.
Results and discussion
Test results
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- Decrease in PCE/NCE ratio
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- Range-finding Toxicity Test:
In animals dosed with test material via the intraperitoneal route there were no premature deaths, however the clinical signs observed were so severe that the animals were killed in extremis in the interests of animal welfare. Clinical signs were only observed at 2000 mg/kg, and they were as follows: loss of righting reflex, decreased respiratory rate, laboured respiration, ptosis, hypothermia, dehydration, occasional body tremors and increased salivation.
In animals dosed with the test material via the oral route no premature deaths or clinical signs were observed.
The test material showed no marked difference in its toxicity to male or female mice, it was therefore considered to be acceptable to use males only for the main test. Adequate evidence of test material toxicity was demonstrated via the intraperitoneal route of administration, therefore, this was selected for use in the main test. A Maximum Tolerated Dose (MTD) for the test material of 1000 mg/kg, was selected for use in the main test, with 250 and 500 mg/kg as the lower dose levels.
Micronucleus Test:
Mortality Data and Clinical Observations
There were no premature deaths or clinical signs seen in any of the dose groups.
Evaluation of Bone Marrow Slides
A summary of the results of the micronucleus test is given in attached Table 1. Individual and group mean data are presented in attached Tables 2 to 8.
Whilst there were no statistically significant decreases in the PCE/NCE ratio in the 24 or 48-hour test material groups when compared to their concurrent vehicle control groups, it should be noted that a marked decrease was observed in the 48-hour test material group. This was taken to indicate that systemic absorption had occurred and exposure to the target tissue, bone marrow, was achieved.
There were no statistically significant increases in the frequency of micronucleated PCEs in any of the test material dose groups when compared to their concurrent vehicle control groups.
The positive control group showed a marked increase in the incidence of micronucleated polychromatic erythrocytes hence confirming the sensitivity of the system to the known mutagenic activity of cyclophosphamide under the conditions of the test.
The test material was found not to produce a significant increase in the frequency of micronuclei in polychromatic erythrocytes of mice under the conditions of the test.
Any other information on results incl. tables
Range-finding Toxicity Test
In animals dosed with test material via the intraperitoneal route there were no premature deaths, however the clinical signs observed were so severe that the animals were killed in extremis in the interests of animal welfare. Clinical signs were only observed at 2000 mg/kg, and they were as follows: loss of righting reflex, decreased respiratory rate, laboured respiration, ptosis, hypothermia, dehydration, occasional body tremors and increased salivation.
In animals dosed with the test material via the oral route no premature deaths or clinical signs were observed. The test material showed no marked difference in its toxicity to male or female mice, it was therefore considered to be acceptable to use males only for the main test. Adequate evidence of test material toxicity was demonstrated via the intraperitoneal route of administration, therefore, this was selected for use in the main test.
A Maximum Tolerated Dose (MTD) for the test material of 1000 mg/kg, was selected for use in the main test, with 250 and 500 mg/kg as the lower dose levels.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
The mutagenicty potential of the test material was assessed according to OECD Guideline 474. The test material was considered to be non-genotoxic under the conditions of the test. - Executive summary:
The study was performed to assess the potential of the test material to produce damage to chromosomes or aneuploidy when administered to mice according to OECD TG 474. The micronucleus test was conducted using the intraperitoneal route in groups of seven mice (males) using the maximum tolerated dose (MID) 1000 mg/kg with 250 and 500 mg/kg as the two lower dose levels. Animals were killed 24 or 48 hours later, the bone marrow was extracted, and smear preparations made and stained. Polychromatic (PCE) and normochromatic (NCE) erythrocytes were scored for the presence of micronuclei. Further groups of mice were given a single intraperitoneal dose of arachis oil (7 mice) or dosed orally with cyclophosphamide (5 mice), to serve as vehicle and positive controls respectively. Vehicle control animals were killed 24 or 48 hours later, and positive control animals were killed after 24 hours. Whilst no statistically significant decreases in the PCE/NCE ratio were observed in the 24 or 48-hour test material dose groups when compared to their concurrent control groups, it should be noted that a marked reduction was observed in the 48-hour 1000 mg/kg test material group. With no premature deaths or clinical signs being observed this was taken to indicate that systemic absorption had occurred. There was no evidence of a significant increase in the incidence of micronucleated polychromatic erythrocytes in animals dosed with the test material when compared to the concurrent vehicle control groups. The test material was considered to be non-genotoxic under the conditions of the test.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.