Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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.
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: 278-928-2 | CAS number: 78491-02-8
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Well reported study performed under GLP and following a standard test method. Test concentrations selected based on toxicity seen in a separate cytotoxicity study.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 989
- Report date:
- 1989
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
Test material
- Reference substance name:
- 1-[1,3-bis(hydroxymethyl)-2,5-dioxoimidazolidin-4-yl]-1,3-bis(hydroxymethyl)urea
- EC Number:
- 278-928-2
- EC Name:
- 1-[1,3-bis(hydroxymethyl)-2,5-dioxoimidazolidin-4-yl]-1,3-bis(hydroxymethyl)urea
- Cas Number:
- 78491-02-8
- Molecular formula:
- C8H14N4O7
- IUPAC Name:
- 1-[1,3-bis(hydroxymethyl)-2,5-dioxoimidazolidin-4-yl]-1,3-bis(hydroxymethyl)urea
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
Constituent 1
Method
Species / strain
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor 1254 induced rat liver S9 mix.
- Test concentrations with justification for top dose:
- Without S9 mix: 0.25, 0.5, 1.0, 1.5 microg/ml.
With S9 mix, 12h harvest: 0.25, 0.5, 1.0, 1.5 microg/ml.
With S9 mix, 18h harvest: 0.25, 0.5, 1.0, 1.5 microg/ml. - Vehicle / solvent:
- Water
Controls
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- triethylenemelamine
- cyclophosphamide
- Details on test system and experimental conditions:
- Without S9 mix: 10h exposure (covering cell cycle), harvested 2h later.
With S9 mix: 2h exposure, harvested 10 and 16h later.
Duplicate cultures, 100 metaphases/culture scored. - Statistics:
- % aberrant cells compared by Fisher's exact test.
Results and discussion
Test results
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Remarks:
- Test culture and control Mitotic Indices were similar. However in a separate (GLP compliant) cytotoxicity study performed in the same laboratory 6h exposure at 0.5 microg/ml without S9 mix or 2h exposure at 0.5 microg/ml reduced MI.
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- A separate study of cytotoxicity to CHO cells had been performed in the same test laboratory (under GLP and using similar test methods) to establish suitable test concentrations for this chromosome analysis study. In that rangefinder study, inhibition of cell division was seen:
- without S9 mix (6 or 8h exposure), MI 9.6 in untreated cells, 6.8 in solvent controls, 4.4 at 0.5 microg/ml
- with S9 mix (2 or 4h exposure), MI 10.0 in untreated cells, 6.2 in solvent controls, 4.4 at 0.5 microg/ml.
In a different cytotoxicity study, performed in another laboratory and using CHO cells treated for 5h and harvested 27h later, MI depression was also seen:
- without S9 mix, MI 10.1 in solvent controls versus 6.0, 7.9, 9.6, 8.5, 7.8, 1.3 at 0.5, 1, 5, 10, 20, 40 microg/ml respectively
- with S9 mix, MI 3.2 in solvent controls versus 7.5, 7.2, 7.4, 9.1, 0.2, 0 at 1, 5, 10, 20, 40, 80 microg/ml respectively.
Any other information on results incl. tables
Group mean results
Test substance (microg/ml) |
–S9 mix |
+S9 mix (12h harvest) |
+S9 mix (18h harvest |
|||
MI |
%Aberrant cells |
MI |
%Aberrant cells |
MI |
%Aberrant cells |
|
Untreated |
3.0 |
1 |
4.6 |
0 |
4.8 |
1 |
Solvent controls |
2.6 |
0 |
3.8 |
1 |
4.8 |
0 |
0.25 |
2.4 |
0 |
3.0 |
1 |
3.4 |
1 |
0.5 |
3.2 |
1 |
4.0 |
0 |
4.6 |
1 |
1.0 |
2.9 |
0 |
4.6 |
1 |
4.2 |
0 |
1.5 |
3.1 |
1 |
4.1 |
0 |
4.4 |
0 |
CP control |
- |
- |
2.2 |
10 |
- |
- |
TEM control |
0.7 |
10 |
- |
- |
- |
- |
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
negative with metabolic activation
ambiguous without metabolic activation
No evidence of clastogenic activity was detected in CHO cells.
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.
