Ferrosilicon - reaction mass of iron and iron disilicide and iron silicide and silicon

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro DNA damage and/or repair study

Remarks:

Type of genotoxicity: DNA damage and/or repair

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

28 Nov. - 22 Dec. 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study. Read-across to synthetic amorphous silica.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 482 (Genetic Toxicology: DNA Damage and Repair, Unscheduled DNA Synthesis in Mammalian Cells In Vitro)

Principles of method if other than guideline:

William, G. M.: Chemical Mutagens, 4, 61-79, 1979

GLP compliance:

yes

Type of assay:

DNA damage and repair assay, unscheduled DNA synthesis in mammalian cells in vitro

Test material

Test material information

Constituent 1

Reference substance name:

Silicon dioxide

EC Number:

231-545-4

EC Name:

Silicon dioxide

Cas Number:

7631-86-9

IUPAC Name:

dioxosilane

Details on test material:

- Name of test material (as cited in study report): Cab-O-Sil EH-5:
CAS-Name: Silica, amorphous, fumed, cryst.-free;
CAS-No.: 112945-52-5

- Substance type: inorganic
- Physical state: solid
- Analytical purity: >99%
- Lot/batch No.: 1H049
- Stability under test conditions: stable

Method

Species / strain

Species / strain / cell type:

hepatocytes: primary culture, rat

Metabolic activation:

without

Test concentrations with justification for top dose:

10, 30, 100, 300, and 1000 µg/ml (5 concentrations tested)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO, 1 % final concentration
- Justification for choice of solvent/vehicle: No data

Controls

Untreated negative controls:

yes

Remarks:

untreated media control

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

Positive controls:

yes

Positive control substance:

7,12-dimethylbenzanthracene

Details on test system and experimental conditions:

NUMBER OF REPLICATIONS: 3

INCUBATION TIME: 18 to 20 h in  the presence of silica

NUMBER OF CELLS EVALUATED: 150 (3 x50)

DETERMINATION OF CYTOTOXICITY
- LDH release

Evaluation criteria:

Validity: Positive control with significant increases in net nuclear grain count, and negative control with less than 15 % of the cells in repair state
and solvent control with net nuclear grain count of less than 1.
Statistical significance: increase in mean nuclear count by at least 5 counts over control ==> significant for the specific dose level.
Positive: dose-related increase and at least one dose with significant increase or
positive: significant increases at two successive doses in the absence of a dose response.
Equivocal: significant increase at one doses in the absence of a dose response.

Results and discussion

Test results

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: 260 - 500 µg/ml: rel. toxicity approx. 50 %

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: other: Primary rat hepatocytes

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

No dose response was observed.

Average net grain counts per nucleus were <1 in the negative controls and ranged from <1 to 2.1 in the treated cultures.

Average net grain counts per nucleus were 30 - 32 in the positive control.

Average net grain counts per nucleus ranged from 1 to 2.1 in the treated cultures.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative