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Toxicological information

Genetic toxicity: in vitro

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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:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: study in full compliance with OECD Guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guideline
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
GLP compliance:
yes (incl. certificate)
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): NLP#6, Voranol RA800
- Molecular weight (if other than submission substance): (average Mn = 280 g/mol)

- Physical state: liquid
- Analytical purity: no data

Method

Target gene:
not applicable
Species / strain
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Metabolic activation system:
S9: isolated from Arochlor 1254 male Sprague Dawley rat liver microsomal fraction
Test concentrations with justification for top dose:
5, 25, 75, 175, 350, 700, 1400, 2800 µg/ml
Vehicle / solvent:
deionized water
Controlsopen allclose all
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
mitomycin C
Remarks:
without S9 mix

Migrated to IUCLID6: 0.1 µg/ml (4 h treatment) and 0.03 µg/ml (18 h treatment)
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
with S9 mix

Migrated to IUCLID6: 2 µg/ml
Details on test system and experimental conditions:
Chromosomes were prepared 18 and 30 hours (for 4 hour treatment) or 18 hours (for 18 hour treatment) after start of treatment with test substances. The treatment interval was 4 hours with and without metabolic activation and 18 hours without metabolic activation. In each experimental group two paralell cultures were set up. Per culture 100 metaphases were scored for structural chromosomal aberrations. Polyploid metaphases were recorded.
Evaluation criteria:
A test was considered positive if there was a relevant and statistically significant increase in the aberration rate.
Statistics:
Statistical significance at the 5% level (p<0.05) was evaluated by means of the chi-square test. Evaluation was performed only for cells carrying aberrations exclusive gaps.

Results and discussion

Test results
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: see additional remarks on results
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Cytotoxicity was observed at 2100 µg/ml and above in the 18 hour cultures without S9 mix only. With S9 mix no cytotoxic effects were observed.
Reference mutagens showed the expected results.
- Effects on pH: slight increase of pH from 7.6 in the vehicle control to about 8.6 in the test substance cultures
- Effects of osmolality: no effects
- Water solubility: soluble up to at least 280 mg/ml
- Precipitation: none
None of the cultures treated with ethylenediamine, +EO +PO in the absence and in the presence of S9 mix showed biologically relevant or statistically significant increased numbers of aberrant metaphases.

Applicant's summary and conclusion