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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro cytogenicity / micronucleus study
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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was conducted according to an appropriate OECD test guideline. GLP compliance is not claimed in the publication. Read across to the registered substance is considered scientifically justified, The original study and the read across are considered reliability 2.

Data source

Reference
Reference Type:
publication
Title:
In vitro genotoxicity assessment of MTES, GPTES and TEOS, three precursors intended for use in food contact coatings
Author:
Lionti, K; Séverin, I; Dahbi, L; Toury, B; Chagnon, M-C
Year:
2014
Bibliographic source:
Food Chem Toxicol 2014 Mar 2;65:76-81

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD 487
GLP compliance:
not specified
Type of assay:
in vitro mammalian cell micronucleus test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
- Name of test material (as cited in study report): 3-glycidoxypropyltriethoxysilane (GPTES), CAS 2602-34-8
- Substance type: monoconstituent
- Physical state: no information
- Analytical purity: no information
- Impurities (identity and concentrations): no information
- Stability under test conditions: the substance known to be reactive with water
- Storage condition of test material: no information

Method

Species / strain
Species / strain / cell type:
mammalian cell line, other: HepG2 cells
Details on mammalian cell type (if applicable):
- Type and identity of media: Minimal Essential Medium
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: no data
- Periodically "cleansed" against high spontaneous background: no data
Additional strain / cell type characteristics:
other: human cell line from the European Collection of Cell Culture, UK.
Metabolic activation:
with and without
Metabolic activation system:
Phenobarbital/beta-naphthoflavone induced rat liver S9
Test concentrations with justification for top dose:
with metabolic activation: 0.03, 0.06, 0.125, 0.25, 0.5 µg/ml; without metabolic activation: 0.03, 0.06, 0.125, 0.25 µg/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: Vinblastine 0.625 ng/ml
Remarks:
without metabolic activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
10 µg with metabolic activation
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

ACTIVATION: Phenobarbital/beta-naphthoflavone induced rat liver S9. S9 mix: final concentration in medium 2% S9; co-factors 5mM glucose-6-phosphate, 0.3 mM NADP, 1.5 mM KCl.

DURATION
- Exposure duration: 3 h with metabolic activation, 24 h without metabolic activation
- Expression time (cells in growth medium): 44 h in medium containing cytochalasin (4 µg/ml). 1 h before harvest cells were washed and re-fed MEM

SPINDLE INHIBITOR (cytogenetic assays): cytochalasin

NUMBER OF REPLICATIONS: duplicate treatments

NUMBER OF CELLS EVALUATED: Micronucleus frequency determined in at least 2000 cells (at least 1000 from each culture). Micronuclei criteria: diameter < one third of main nucleus; clearly distinguishable from main nucleus and staining identical to main nucleus.

DETERMINATION OF CYTOTOXICITY
- Method: other: cytokinesis-block proliferation index (CBPI). CBPI =[(the number of cells with 1 nucleus x 1)+(the number of cells with greater than 2 nuclei x 3)]/total number of cells scored

Evaluation criteria:
According to OECD487
Statistics:
One-way ANOVA followed by Student-Newman-Keuls test, and the differences were considered significant for p less than 0.05.

Results and discussion

Test results
Species / strain:
mammalian cell line, other: HepG2 cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
50 % cytotoxicity at highest concentration in absence of metabolic activation
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid

Any other information on results incl. tables

The results in the paper are presented in the form of bar charts. The numbers in the table below have been estimated from the charts.

Table 1 Results of micronucleus assay for GPTES 

Concentration

MN/1000 BNC

Cytotoxicity (%)

-MA

+MA

-MA

+MA

Solvent control

12

10

0

0

0.03

13

13

-6

0

0.06

11

13

-10

0

0.125

14

14

-3

0

0.25

12

12

50

2%

0.5

NT

11

NT

25%

Positive control

55

33

4

0

NT not tested

MN micronuclei

BNC binucleated cells

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative with and without metabolic activation

[3-(2,3-epoxypropoxy)propyl]triethoxysilane has been tested for ability to induce formation of micronuclei in a study conducted according to OECD 478. No evidence of test-substance induced micronucleus formation was observed in HepG2 cells in either the presence or the absence of metabolic activation. Appropriate positive and solvent controls were included and gave expected results. It is concluded that the test substance in negative for cytogenicity under the conditions of the test.