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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 238-925-9 | CAS number: 14858-73-2
- 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
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:
- 2004-10-27 to 2004-12-14
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 005
- Report date:
- 2005
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- adopted July 21, 1997
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- June 08, 2000
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5395 (In Vivo Mammalian Cytogenetics Tests: Erythrocyte Micronucleus Assay)
- Version / remarks:
- EPA 712-C-98-226, August 1998
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- Bis(2-ethylhexyl) carbonate
- EC Number:
- 238-925-9
- EC Name:
- Bis(2-ethylhexyl) carbonate
- Cas Number:
- 14858-73-2
- Molecular formula:
- C17H34O3
- IUPAC Name:
- bis(2-ethylhexyl) carbonate
- Test material form:
- other: liquid
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: minimum 7 weeks
- Weight at study initiation: males: 30.0 - 36.0 g, females 24.0 - 30.0 g
- Assigned to test groups randomly: yes
- Fasting period before study: no data
- Housing: 5 animals of identical sex per cage, Macrolon Type III (Hereto), granulated soft wood bedding (ALTROMIN)
- Diet: in all probability ad libitum, standard laboratory pelleted mouse diet (ALTROMIN)
- Water: ad libitum, tap water
- Acclimation period: minimum of 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19- 25
- Humidity (%): 55 +/- 10
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): artificial light 6:00 - 18:00
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- - Vehicle(s)/solvent(s) used: cotton seed oil
- Justification for choice of solvent/vehicle: The solvent was chosen according to its relative non-toxicity for the animals.
- Concentration of test material in vehicle: 200 mg/mL - Details on exposure:
- The test item was prepared and diluted in cotton seed oil within 1 h before treatment.
At the beginning of the experiment the animals were individually weighed and the administered volume adjusted to the animal's body weight. The animals received the test item once ip. - Duration of treatment / exposure:
- The animals received the test item once ip.
Sampling of the bone marrow was carried out on animals 24 and 48 h after treatment. - Frequency of treatment:
- single exposure
- Post exposure period:
- 24 and 48 hours
Doses / concentrations
- Remarks:
- Doses / Concentrations:
2000 mg/kg bw
Basis:
actual ingested
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide, purity: at least 98%
- Justification for choice of positive control(s): not given, however, cyclophosphamide is a standard positive control substance recommended by the guidelines
- Route of administration: single i.p.
- Doses / concentrations: 40 mg/kg bw dissolved in 0.9% NaCl, application volume 10 mL/kg bw
Examinations
- Tissues and cell types examined:
- bone marrow cells
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
The selection of the highest applied dose based on the results of the pre-experiment for toxicity. The main experiment was performed as a limit test
with 2000 mg/kg bw.
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):
24 h preparation interval: 2000 mg/kg bw, diluted in cotton seed oil, application volume 10 mL/kg bw
48 h preparation interval: 2000 mg/kg bw, diluted in cotton seed oil, application volume 10 mL/kg bw
DETAILS OF SLIDE PREPARATION:
Bone marrow was obtained from the femurs immediately following sacrifice by cervical dislocation of the animals. Cells were removed from the femurs by cutting off the epiphyses and by flushing the marrow out with fetal calf serum using a 5 ml syringe. The cell suspension was centrifuged at 200 x g for 10 minutes and the supernatant was discarded. A drop of the resuspended cell pellet was spread on a slide as a smear. This was air-dried and stained with May-Grünwald/Giemsa. At least one slide was made from each bone marrow sample.
METHOD OF ANALYSIS:
All slides, including those of positive and negative controls, were coded before microscopic analysis. Evaluation of the slides was performed using microscopes with 100 x oil immersion objectives. 2000 immature erythrocytes per animal were scored for the incidence of micronucleated immature erythrocytes. To detect an eventually occurring cytotoxic effect of the test item the ratio between immature and mature erythrocytes was determined. At least 200 immature erythrocytes were counted per animal and the result was expressed as relative PCE (reI. PCE = proportion of polychromatic (immature) erythrocytes among total erythrocytes). - Evaluation criteria:
- EVALUATION OF RESULTS
There are several criteria for determining a positive result:
- dose-related increase in the number of micronucleated cells and/or
- biologically relevant increase in the number of micronucleated cells for at least one of the dose groups.
According to the OECD guideline, the biological relevance as well as the statistical significance of the results are the criterion for the interpretation.
A test item is considered to be negative if there is no biological relevant and/or statistical significant increase in the number of micronucleated cells at any dose level. However, both biological relevance and statistical significance will be considered together.
ACCEPTANCE CRITERIA
The data generated are considered acceptable if:
- at the commencement of the study, the weight variation of animals should be minimal and not exceed ± 20% of the mean weight of each sex,
- the background frequency of micronucleated cells is in the normal range as reported in the literature or within the laboratory's historical range,
- the test system is sensitive to the known mutagen as judged by the results in the concurrent positive control animals. - Statistics:
- For the statistics the nonparametric Mann-Whitney test was used.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
The test item was suspended in cotton seed oil. 200 mg/mL of the test item was used as highest dose group corresponding to 2000 mg/kg bw according to the OECD guideline 474. The volume administered was 10 mL/kg bw ip. Three male and three female mice were treated with the test item. No
systemic toxicity was observed in any of the animals evaluated. The animals survived 72 h after the treatment.
The selection of the highest dose was conducted in accordance with the following current international guidelines for assessment of acute toxicity
(OECD 420 and 423), particularly with respect to selection of dose spacing and animal welfare aspects.
RESULTS OF DEFINITIVE STUDY
- Toxicity: 2000 mg/kg bw was tested as the maximum dose in the main experiment. The volume administered was 10 mL/kg bw. No toxicity was noted after administration of the test item in any of the animals evaluated up to 48 h.
- Induction of micronuclei (for Micronucleus assay): The negative controls (24 h and 48 h) evaluated were within the range of the historical control data. The mean values of micronuclei observed for the negative control (24 h) were 0.13 % for male and 0.06 % for female mice. The mean values for the 48 h negative control were 0.09 % for the male and 0.13 % for the female mice. The values noted for the dose groups which were treated with the test item (24 h, 48 h) were within the historical control data range. The values noted for the 24 h treatment group were 0.13 % for the male and 0.09 % for the female mice. The animal groups which were treated with the test item and prepared 48 h after the treatment showed mean values of micronuclei of 0.10 % male mice and 0.09 % female mice. All mean values of micronuclei formation noted after treatment with the test item were within the historical control data of the negative control. No biologically relevant increase of micronuclei was found.
- Ratio of PCE/NCE (for Micronucleus assay): The negative controls (24 h, 48 h) were within the historical control range of the negative control. The values noted for the 24 h negative control were 0.54 for the male and 0.58 for the female mice. The values detected for the 48 h negative control were 0.55 for the male and 0.55 for the female mice. The relative PCE of the animal groups, which were treated with 2000 mg/kg bw test item (24 h, 48 h) were within the historical control data. The values noted for the 24 h treatment were 0.50 for the male and 0.54 for the female mice. The animal groups which were treated with 2000 mg/kg bw test item and prepared 48 h after the treatment showed mean values of relative PCE of 0.53 (male mice) and 0.56 (female mice).
- Appropriateness of dose levels and route: application of the limit dose of 2000 mg/kg bw, as recomended by the guidelines
- Statistical evaluation: The nonparametric Mann-Whitney test was performed to verify the results. No statistically significant enhancement (p<0.05) of cells with micronuclei was noted in any dose group of the test item evaluated.
RESULTS OF POSITIVE CONTROL
Cyclophosphamide (40 mg/kg bw) administered ip was used as positive control which induced a significant increase of induced micronucleus frequency (percentage of cells with micronuclei was 2.60 % for male and 2.05 % for female mice). This demonstrates the validity of the assay.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
It can be stated that during the study described and under the experimental conditions reported, the test item Bis(2-ethylhexyl) carbonate did not induce structural and/or numerical chromosomal damage in the immature erythrocytes of the mouse.
Therefore, Bis(2-ethylhexyl) carbonate is considered to be non-mutagenic in the Mammalian Erythrocyte Micronucleus Test. - Executive summary:
In a NMRI mouse bone marrow micronucleus assay according to OECD Guideline No. 474, July 21, 1997, EU Method B12, June 08, 2000 and US EPA Guideline OPPTS 870.5395, EPA 712-C-98-226, August 1998, 5 male and 5 female animals/harvest time were treated i.p. with Bis(2-ethylhexyl) carbonate (99-100 % a.i.) at the limit dose of 2000 mg/kg bw. Bone marrow cells were harvested at 24 and 48 hours post-treatment. The vehicle was cotton seed oil.
There were no signs of toxicity during the study. Bis(2-ethylhexyl) carbonate was tested at an adequate dose, as the tested dose is the limit dose recommended by the guidelines. The positive control induced the appropriate response.
There was no 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 of the mentioned guidelines for in vivo cytogenetic mutagenicity data.
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.