Registration Dossier
Registration Dossier
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: 218-218-1 | CAS number: 2082-81-7
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.
NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.
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.
