Silicon

Genetic toxicity: in vitro

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:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well conducted, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Micronucleus formation in V79 cells treated with respirable silica dispersed in medium and in simulated pulmonary surfactant.

Author:

Liu, X., M. J. Keane, et al.

Year:

1996

Bibliographic source:

Mutat Res.361(2-3): 89-94.

Materials and methods

Principles of method if other than guideline:

An in vitro micronucleus assay on Chinese hamster fibroblasts was performed. Two particle sizes of crystalline quartz and non-crystalline silica (5 μm Spherisorb®) were assayed for induction of micronuclei (MN).

GLP compliance:

no

Type of assay:

in vitro mammalian cell micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

Spherisorb® (non-crystalline silica)

IUPAC Name:

Spherisorb® (non-crystalline silica)

Details on test material:

- particle size: 5 μm (Spherisorb®)
- in addition, crystalline silica (quartz) was studied

Method

Species / strain

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

without

Test concentrations with justification for top dose:

0, 20, 40, 80, 160 microg/cm2

Vehicle / solvent:

no vehicle

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

no

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: N-METHYL-N'-NITRO-N-NITROSOGUANIDINE

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 24 h
- Expression time (cells in growth medium): 24 h
- Fixation time (start of exposure up to fixation or harvest of cells): 48 h

NUMBER OF CELLS EVALUATED: 3000 cells/treatment

DETERMINATION OF CYTOTOXICITY : determined, but the method not described

Statistics:

Chi-squared test and linear regression

Results and discussion

Test results

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

not applicable

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

not examined

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

The results showed that both crystalline and non-crystalline silica dispersed in medium induced micronuclei formation in a dose-dependent manner. Induction was seen only at dose levels inducing cytotoxicity. Crystalline silica was more active in this assay than non-crystalline silica on a mass basis. The results also show that the frequency of micronucleated cells in cultures treated with lung surfactant-coated crystalline silica was not significantly different from that of the non-treated control cultures. The authors state that the high observed cytotoxicity might explain the genotoxic effect. The pre-treatment of silica particles with simulated pulmonary surfactant reduced cytotoxicity and also reduced or delayed genotoxicity.

Remarks on result:

other: strain/cell type: Chinese hamster lung fibroblasts (V79)

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
other: positive only at cytotoxic concentrations

Synthetic amorphous silica caused micronuclei at cytotoxic concentrations but was less active than crystalline silica.

Executive summary:

Liu et al. (1996) challenged Chinese hamster fibroblasts with respirable silica particles using an in vitro genotoxicity assay. Two particle sizes of crystalline quartz and non-crystalline silica (5 μm Spherisorb®) were assayed for induction of micronuclei (MN). The results showed that both crystalline and non-crystalline silica dispersed in medium induced micronuclei formation in a dose-dependent manner. Induction was seen only at dose levels inducing cytotoxicity. Crystalline silica was more active in this assay than non-crystalline silica on a mass basis. The results also show that the frequency of micronucleated cells in cultures treated with lung surfactant-coated crystalline silica was not significantly different from that of the non-treated control cultures. The authors state that the high observed cytotoxicity might explain the genotoxic effect. The pre-treatment of silica particles with simulated pulmonary surfactant reduced cytotoxicity and also reduced or delayed genotoxicity.