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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian germ cell study: gene mutation
Remarks:
Type of genotoxicity: gene mutation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, sufficiently documented and acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Pulmonary chemokine and mutagenic responses in rats after subchronic inhalation of amorphous and crystalline silica.
Author:
Johnston, C.J. et al.
Year:
2000
Bibliographic source:
Toxicological Sciences 56, 405-413

Materials and methods

Principles of method if other than guideline:
Ex vivo (isolation of cells from treated animals) rat HPRT mutation assay with alveolar epithelial cells after 13 weeks inhalation exposure.
GLP compliance:
not specified
Type of assay:
endogenous gene animal assay

Test material

Constituent 1
Reference substance name:
112945-52-5
EC Number:
601-216-3
Cas Number:
112945-52-5
IUPAC Name:
112945-52-5
Details on test material:
- Name of test material (as cited in study report): Aerosil 200 Degussa, amorphous silica
- Analytical purity: no data

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male

Administration / exposure

Route of administration:
inhalation: aerosol
Vehicle:
filtered air
Details on exposure:
TYPE OF INHALATION EXPOSURE: whole body


GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: compartmentalized 300-liters horizontal laminar flow chambers
- System of generating particulates/aerosols: a screw-feed mechanism in combination with a Venturi-type dust feeder.
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
6 h/day, 5 days/week for 13 weeks
Post exposure period:
none
Doses / concentrations
Remarks:
Doses / Concentrations:
50.4 ± 19.9 mg/m3
Basis:
analytical conc.
No. of animals per sex per dose:
4
Control animals:
yes, concurrent vehicle

Examinations

Tissues and cell types examined:
rat alveolar type-II cells
Details of tissue and slide preparation:
METHOD OF ANALYSIS:
Selection for mutation in the HPRT gene in cells isolated from treated animals. Isolated cells were seeded in flasks. After removal of non-adherent cells, cell cultures were fed with selection medium containing 6-thioguanine (40 µM); cultures were refed every other day with 6-TG-containing medium. After 14 - 21 days in culture the cells were fixed and immunostained with an antibody to cytokeratins 8, 18 and 19 and 6-TG-resistant cytokeratin staining colonies of greater than 50 cells counted.
Statistics:
Analysis of variance. Differenced from the control group were determined using Dunnett's test. Statistical significance was considered at p < 0.05.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid

Any other information on results incl. tables

Mutation frequencies in the air control group were 7.6 ± 3.4 mutants/106 epithelial cells. No significant changes in the HPRT mutation frequency compared to controls were observed for alveolar epithelial cells from rats exposed to 50 mg/m3 amorphous silica after 13 weeks.

Applicant's summary and conclusion