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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:
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

Reference
Name:
Unnamed
Type:
Constituent
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.