1,3-Propanediol, 2-methyl-, reaction products with ethenyltrimethoxysilane

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16 Jun - 07 Jul 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2010

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Deviations:

no

GLP compliance:

not specified

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

1,3-Propanediol, 2-methyl-, reaction products with ethenyltrimethoxysilane

EC Number:

700-957-0

Cas Number:

1141852-17-6

Molecular formula:

UVCB

IUPAC Name:

1,3-Propanediol, 2-methyl-, reaction products with ethenyltrimethoxysilane

Constituent 2

Reference substance name:

Reaction products of trimethoxy(vinyl)silane and 2-methylpropane-1,3-diol (2:5-6)

IUPAC Name:

Reaction products of trimethoxy(vinyl)silane and 2-methylpropane-1,3-diol (2:5-6)

Details on test material:

- Name of test material (as cited in study report): Y-15866
- Physical state: liquid
- Analytical purity: 72%
- Lot/batch No.: 3710-10
- Stability under test conditions: at room temperature

Method

Target gene:

Not applicable

Species / strain

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Details on mammalian cell type (if applicable):

- Type and identity of media: MEM (Biochrom, Berlin, Germany) with Fetal Bovine Serum Standard Quality (PAA Laboratories GmbH, Cölbe, Germany)
- Properly maintained: yes

Metabolic activation:

with and without

Metabolic activation system:

co-factor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of 8-12 weeks old male Wistar Hsd Cpb: WU rats induced with 80 mg/kg bw phenobarbital i.p. and ß-naphthoflavone p.o. each on three consecutive days

Test concentrations with justification for top dose:

Experiment I: 4 h treatment with and without S9 mix
Cytotoxicity testing: 2.4, 4.9, 9.8, 19.5, 39.1, 78.1, 156.3, 312.5, 625, 1250, 2500 and 6950 µg/mL
Chromosome aberration analysis: 156.3, 312.5, 2500 and 6950 µg/mL (with S9); 312.5, 1250, 2500 and 6950 µg/mL (without S9)

Experiment II: 4 h treatment with S9 mix and 18 h without S9 mix
Cytotoxicity testing: 19.5#, 39.1, 78.1, 156.3, 312.5, 625, 1250, 2500 and 6950 µg/mL (#this concentration was additionally analysed in the absence of S9)
Chromosome aberration analysis: 39.1, 625#, 1250, 2500 and 6950 µg/mL (#this concentration was additionally analysed in the presence of S9)

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

tetrahydrofuran (THF)

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: -S9: ethyl methanesulfonate (EMS), 1000 (Exp. I) and 600 (Exp. II) µg/mL; +S9: cyclophosphamide (CPA), 1.4 (Exp. I) and 1.0 (Exp. II) µg/mL

Results and discussion

Test results

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Under the experimental conditions reported, the test substance did not induce structural chromosome aberrations in V79 cells (Chinese hamster cell line).

Executive summary:

The test substance Y-15866 was assayed in an in vitro mammalian chromosome aberration test conducted in accordance with GLP and similar to OECD guideline 473. In two independent experiments, V79 Chinese hamster cells were treated with the test substance at concentrations up to 6950 µg/mL, with and without metabolic activation system (S9 mix). In the first experiment, continuous treatment with the test substance for 4 h followed by a 14 h-recovery period was performed. Since no clear cytotoxicity indicated by reduced mitotic indices or reduced cell numbers was observed up to the highest concentration, 6950 µg/mL was chosen as top treatment concentration in Experiment II. In this experiment, cells were analogously treated with the test substance in the presence of S9 (4 h + 14 h recovery period). In contrast, cells were continuously treated for a period of 18 h without recovery period in the absence of S9 mix. Since no dose-response relationship was observed for cytotoxic effects in both experiments, concentrations used for evaluation of chromosome aberrations were selected based on the highest non-cytotoxic concentration tested. Thus, concentrations chosen for chromosome analysis ranged from 156.3 to 6950 µg/mL in Experiment I and 39.1 to 6950 µg/mL in Experiment II. In both experiments, no biologically relevant increase in the number of cells carrying structural chromosome aberrations was observed after treatment with the test substance in the absence and presence of S9 mix. The positive control substances yielded the expected results. Under the conditions of this chromosome aberration assay, it was concluded that Y-15866 did not show clastogenic activity in V79 Chinese hamster cells.