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: 298-364-0 | CAS number: 93803-89-5
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:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Study period:
- 01 Feb - 21 Apr 1999
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study with acceptable restrictions (no data on analytical purity).
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 999
- Report date:
- 2000
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- yes
- Remarks:
- No details on the purity of the test substance
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- yes
- Remarks:
- No details on the purity of the test substance
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- The Department of Health of the Government of the United Kingdom
- Type of assay:
- in vitro mammalian chromosome aberration test
Test material
- Reference substance name:
- 131459-39-7
- Cas Number:
- 131459-39-7
- IUPAC Name:
- 131459-39-7
- Details on test material:
- - Physical state: straw colored liquid
- Analytical purity: no data
- Storage condition of test material: RT in the dark
Constituent 1
Method
- Target gene:
- Not applicable
Species / strain
- Species / strain / cell type:
- lymphocytes:
- Metabolic activation:
- with and without
- Metabolic activation system:
- Arochlor 1254 induced S9-Mix from male Spraque-Dawley rats
- Test concentrations with justification for top dose:
- 1. Experiment:
4(20) h without S9: 39.06; 78.13; 156.25; 312.5; 625; 1250; 2500; 5000 µg/mL
4(20) h with S9: 39.06; 78.13; 156.25; 312,5; 625; 1250; 2500; 5000 µg/mL
2. Experiment
24 h without S9: 39.06; 78.13; 156.25; 312,5; 625; 1250; 2500; 5000 µg/mL
4(20) h with S9: 39.06; 78.13; 156.25; 312,5; 625; 1250; 2500; 5000 µg/mL - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: acetone
Controlsopen allclose all
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- acetone
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- in absence of S9-Mix
Migrated to IUCLID6: 750 µg/mL
- Negative solvent / vehicle controls:
- yes
- Remarks:
- acetone
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- in presence of S9-Mix
Migrated to IUCLID6: 25 µg/mL
- Details on test system and experimental conditions:
- Duplicate cultures of human lymphocytes were evaluated for chromosome aberrations at up to three dose levels. For each experiment, whole blood was drawn from the peripheral circulation of a volunteer who had previously been screened for suitability. The cell cycle length of approx. 14 h was determined by BrdU incorporation.
METHOD OF APPLICATION: in medium (Eagle´s minimal essential medium with HEPES buffer supplemented with L-glutamine, Pen/Strep, amphotericin B and 15% FCS
DURATION
- Exposure duration: Experiment I: 4 h with or without S9 mix .
- Experiment II: Either 4 h with S9 mix or 24 h without S9 mix.
- Expression time (cells in growth medium): 20 h after 4 h exposure to the test substance and 20 h expression time
SPINDLE INHIBITOR (cytogenetic assays): Colcemid (0.1 µg/mL)
STAIN (for cytogenetic assays): 5% Gurrs Giemsa for 5 min
NUMBER OF REPLICATIONS: 2
NUMBER OF CELLS EVALUATED: 200
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index - Evaluation criteria:
- All vehicle (solvent) controls had frequencies of cells with aberrations within the range expected for normal human lymphocytes. All the positive control materials induced statistically significant increases in the frequency of cells with aberrations indicating the satisfactory performance of the test and of the activity of the metabolising system.
- Statistics:
- The frequency of cells with aberrations and the frequency of polyploid cells was compared, where necessary, with the concurrent vehicle control value using Fisher´s Exact test.
Results and discussion
Test resultsopen allclose all
- Species / strain:
- lymphocytes:
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Remarks:
- at and above 1250 µg/mL
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- lymphocytes:
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Remarks:
- at and above 1250 µg/mL
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: Medium was "cloudy" from 156.25 µg/mL and a precipitate was seen from 1250 µg/mL without effects on the toxicity responsefects:
COMPARISON WITH HISTORICAL CONTROL DATA: Yes, data were in range with the historical control data. - Remarks on result:
- other: strain/cell type: lymphocytes
- Remarks:
- Migrated from field 'Test system'.
Any other information on results incl. tables
Table 1: Experiment 1: 4 h treatment without metabolic activation
Treatment group (µg/ml) |
Number of cells scored |
Total gaps |
Chromatid |
Chromosome |
others |
Total abberations |
Abberant cells |
||||
Breaks |
Exchanges |
Breaks |
Exchanges |
x |
(+Gaps) |
(+Gaps) |
(+Gaps) |
(+Gaps) |
|||
Vehicle control |
200 |
5 |
0 |
1 |
0 |
1 |
0 |
7 |
2 |
7 |
2 |
1250 |
200 |
5 |
0 |
0 |
3 |
0 |
0 |
8 |
3 |
8 |
3 |
2500 |
200 |
2 |
2 |
0 |
0 |
0 |
0 |
4 |
2 |
4 |
2 |
5000 |
200 |
5 |
4 |
0 |
0 |
1 |
0 |
10 |
5 |
9 |
5 |
EMS 750 |
200 |
24 |
9 |
5 |
5 |
0 |
0 |
43 |
19 |
35 |
17 |
Table 2: Experiment 1: 4 h treatment with metabolic activation
Treatment group (µg/ml) |
Number of cells scored |
Total gaps |
Chromatid |
Chromosome |
others |
Total abberations |
Abberant cells |
||||
Breaks |
Exchanges |
Breaks |
Exchanges |
x |
(+Gaps) |
(+Gaps) |
(+Gaps) |
(+Gaps) |
|||
Vehicle control |
200 |
4 |
1 |
0 |
0 |
0 |
0 |
5 |
1 |
4 |
1 |
1250 |
200 |
6 |
4 |
0 |
0 |
0 |
0 |
10 |
4 |
9 |
4 |
2500 |
200 |
4 |
2 |
0 |
0 |
0 |
0 |
6 |
2 |
5 |
2 |
5000 |
200 |
2 |
4 |
0 |
1 |
0 |
0 |
7 |
5 |
7 |
5 |
CP 25 |
200 |
13 |
12 |
3 |
2 |
0 |
0 |
30 |
17 |
24 |
15 |
Table 3: Experiment 2: 20 h treatment without metabolic activation
Treatment group (µg/ml) |
Number of cells scored |
Total gaps |
Chromatid |
Chromosome |
others |
Total abberations |
Abberant cells |
||||
Breaks |
Exchanges |
Breaks |
Exchanges |
x |
(+Gaps) |
(+Gaps) |
(+Gaps) |
(+Gaps) |
|||
Vehicle control |
200 |
2 |
2 |
1 |
0 |
0 |
0 |
5 |
3 |
5 |
3 |
1250 |
200 |
7 |
0 |
0 |
1 |
0 |
0 |
8 |
1 |
8 |
1 |
2500 |
200 |
0 |
1 |
0 |
0 |
0 |
0 |
1 |
1 |
1 |
1 |
5000 |
200 |
6 |
0 |
0 |
0 |
0 |
0 |
6 |
0 |
6 |
0 |
EMS 500 |
200 |
53 |
41 |
13 |
2 |
0 |
0 |
109 |
56 |
74 |
48 |
Table 4: Experiment 2: 4 h treatment with metabolic activation
Treatment group (µg/ml) |
Number of cells scored |
Total gaps |
Chromatid |
Chromosome |
others |
Total abberations |
Abberant cells |
||||
Breaks |
Exchanges |
Breaks |
Exchanges |
x |
(+Gaps) |
(+Gaps) |
(+Gaps) |
(+Gaps) |
|||
Vehicle control |
200 |
0 |
0 |
0 |
2 |
0 |
0 |
2 |
2 |
2 |
2 |
1250 |
200 |
4 |
2 |
2 |
3 |
0 |
0 |
9 |
5 |
7 |
3 |
2500 |
200 |
5 |
2 |
0 |
1 |
0 |
0 |
8 |
3 |
8 |
3 |
5000 |
200 |
3 |
2 |
0 |
2 |
0 |
0 |
7 |
4 |
6 |
3 |
CP 25 |
200 |
10 |
10 |
2 |
0 |
0 |
0 |
22 |
12 |
15 |
11 |
The test substance was non-clastogenic to human lymphocytes in vitro.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
negative
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.
