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EC number: 218-218-1 | CAS number: 2082-81-7
- 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
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- Flash point
- Auto flammability
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- 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
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- Nanomaterial pour density
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- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
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- 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
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- 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:
- 1998-03-25 to 1998-05-03
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 998
- Report date:
- 1998
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- draft version 1997
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- 29 December 1992
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- Tetramethylene dimethacrylate
- EC Number:
- 218-218-1
- EC Name:
- Tetramethylene dimethacrylate
- Cas Number:
- 2082-81-7
- Molecular formula:
- C12H18O4
- IUPAC Name:
- butane-1,4-diyl bis(2-methylacrylate)
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): 1,4-Butanediol dimethacrylate
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Winkelmann, Borchen, Germany
- Age at study initiation: no data
- Weight at study initiation: 26 – 36 g
- Assigned to test groups randomly: yes
- Fasting period before study: no data
- Housing: 5 animals of identical sex per cage
- Diet (e.g. ad libitum): pellet standard diet (Altromin)
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25°C
- Humidity (%): 55+/-10°C
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light):12/12
IN-LIFE DATES: no data
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: cotton seed oil
- Justification for choice of solvent/vehicle: relatively nontoxic to the animals
- Concentration of test material in vehicle:
- Amount of vehicle (if gavage or dermal): 16.7 mL/kg bw
- Lot/batch no. (if required): 27H0534
- Purity: no data - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
dilution in cotton seed oil; single standard volume of 16.7 mL/kg bw - Duration of treatment / exposure:
- The animals received the test item once. Sampling of the bone marrow was carried out on animals 24 and 48 h after treatment.
- Frequency of treatment:
- single dose
- Post exposure period:
- The animals were sacrificed 24 and 48 hours after treatment.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 200 mg/kg bw/day (actual dose received)
- Remarks:
- 24 h interval
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- Remarks:
- 24 h interval
- Dose / conc.:
- 2 000 mg/kg bw/day (actual dose received)
- Remarks:
- 24 h interval
- Dose / conc.:
- 2 000 mg/kg bw/day (actual dose received)
- Remarks:
- 48 h interval
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide
- Justification for choice of positive control(s): appropriate reference mutagen
- Route of administration: single administration i.p.
- Doses / concentrations: 30 mg/kg bw in 0.9% NaCl (10 mL/kg bw)
Examinations
- Tissues and cell types examined:
- bone marrow erythrocytes (polychromatic erythrocytes)
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
dose selection based on acute toxicity pre-test: at 2000 mg/kg bw no toxic signs were found two lower dose groups (200 and 1000 mg/kg bw) were selected for 24 h treatment interval
DETAILS OF SLIDE PREPARATION:
- removal of femura
- bone marrow was flushed out with 1 mL FCS followed by resuspension of cells and centrifugation at 1500 rpm for 10 min
- cells were resuspended in FCS and smeared on slides
- air drying of slides, staining with May-Grünwald/Giemsa
- at least one slide prepared from each bone marrow sample
METHOD OF ANALYSIS:
- 2000 polychromatic erythrocytes were analysed per animal for micronuclei
- ratio between polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) was determined to assess cytotoxicity (expressed as NCE per 1000 PCE)
- analysis carried out with coded slides - Evaluation criteria:
- A test item is classified mutagenic if it induces either a statistically significant dose related increase in the number of micronucleated PCE or a reproducible statistically significant positive result for at least one test point.
- Statistics:
- non-parametric Mann-Whitney test
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: 2000 mg/kg bw
- Solubility: no data
- Clinical signs of toxicity in test animals: after 1 hour reduced spontaneous activity
- Other: only pre-test for toxicity, no further analysis
RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): no induction of micronuclei over background (see table); the mean values of micronuclei observed after treatment with the test item (0.11% to 0.15%) were in the same range as the negative control groups (0.10% to 0.13%)
- Ratio of PCE/NCE (for Micronucleus assay): slight effect on PCE/NCE ration by treatment with test item at a concentration of 2000 mg/kg bw at 24 and 48 h indicating slight cytotoxic properties
- Statistical evaluation: no significance found for 1000 mg/kg bw (24 h), 2000 mg/kg bw (24 h), 2000 mg/kg bw (48 h); lowest dose of 200 mg/kg bw (24 h) not tested for significance, as values were equal to or lower than negative control
Any other information on results incl. tables
group | sex | mean MN/2000 PCE | %MN | relative to N.C. | PCE/NCE |
N.C. | m | 2 | 0.1 | 1.0 | 1000/808.2 |
P.C. | m | 34.6 | 1.73 | 17.3 | 1000/1045.6 |
test item 2000mg/kg, 24 h | m | 2.6 | 0.13 | 1.3 | 1000/995.2 |
test item 2000mg/kg, 48 h | m | 3 | 0.15 | 1.5 | 1000/1011 |
test item 1000mg/kg, 24 h | m | 2.4 | 0.12 | 1.2 | 1000/868 |
test item 200mg/kg, 24 h | m | 2.2 | 0.11 | 1.1 | 1000/820.2 |
N.C. | f | 2.6 | 0.13 | 1.0 | 1000/844.2 |
P.C. | f | 38.8 | 1.94 | 14.9 | 1000/1055.8 |
test item 2000mg/kg, 24 h | f | 2.4 | 0.12 | 0.9 | 1000/972.8 |
test item 2000mg/kg, 48 h | f | 2.6 | 0.13 | 1.0 | 1000/1016.8 |
test item 1000mg/kg, 24 h | f | 2.8 | 0.14 | 1.1 | 1000/884.4 |
test item 200mg/kg, 24 h | f | 2.4 | 0.12 | 0.9 | 1000/828.6 |
N.C. = negative control
P.C. = positive control
m = male
f = female
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
In this study under the experimental conditions reported, 1,4-BDDMA did not induce micronuclei over background as determined by the micronucleus test in bone marrow cells of the mouse. - Executive summary:
In a NMRI mouse bone marrow micronucleus assay according to OECD guideline 474, draft version 1997, 5 animals per sex per dose were treated by oral gavage (single dose) with 1,4-BDDMA (93.9% a.i.) at doses of 0, 200, 1000 and 2000 mg/kg bw. Bone marrow cells were harvested at 24 h (200, 1000 and 2000 mg/kg dose groups) and 48 h (2000 mg/kg dose group) post-treatment. The vehicle was cotton seed oil.
There were no signs of toxicity during the study based on mortality or clinical signs. A slight effect on the ratio of polychromatic to normochromatic erythrocytes was observed in the 2000 mg/kg dose group 24 and 48 h post-treatment indicating a possible weak toxic effect to the bone marrow. There was no significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow after any treatment time. 1,4-BDDMA was tested at an adequate dose evel which included the guideline limit dose of 2000 mg/kg bw. The positive control induced the appropriate response.
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