Silicic acid, calcium salt

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: gene mutation

Remarks:

Type of genotoxicity: gene mutation

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: Comparable to guideline study, containing scientifically justified modifications, no validated standard test in vivo (see: Method).

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2000

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Method: ex-vivo/in-vitro HPRT assay, no standard guideline available, HPRT part likely based on OECD Guideline 476 (In vitro Mammalian Cell Gene Mutation Test) as well as previous inhalation on OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day, but limited performance, only males, one high exposure level, without comprehensive organtoxicology and pathology as well as without clinical chemistry/haematology etc.

GLP compliance:

not specified

Type of assay:

other: mammalian cell gene mutation assay: ex-vivo/in-vitro HPRT assay

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

Molecular formula:

O2Si

IUPAC Name:

dioxosilane

Details on test material:

- Name of test material (as cited in study report):
Aerosil 200: CAS-Name: Silica, amorphous, fumed, cryst.-free;
CAS-No.: 112945-52-5
(note: specified as "precipitated" in the report, apparently erroneous).

- Substance type: inorganic
- Physical state: solid

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
- Age at study initiation: no data
- Weight at study initiation: 200 - 250 g

no further data

Administration / exposure

Route of administration:

inhalation

Details on exposure:

TYPE OF INHALATION EXPOSURE: whole body

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 300-L horizontal laminar-flow chamber, compartmentalised
- System of generating particulates/aerosols: screw-feed mechanism (ACCURate, Whitewater) in combination with a Venturi-type dust feeder
- Temperature, humidity, pressure in air chamber: no data
- Air flow rate: no data
- Air change rate: no data
- Method of particle size determination: no data



TEST ATMOSPHERE
- Brief description of analytical method used: no data
- Samples taken from breathing zone: no data

Duration of treatment / exposure:

13 wks

Frequency of treatment:

6 h/d, 5 d/wk

Post exposure period:

no, not for this endpoint of the study

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
50 mg/m3
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
50.4 +-19 mg/m3
Basis:
analytical conc.

No. of animals per sex per dose:

no data, only males, probably 4 animals per endpoint

Control animals:

yes, concurrent no treatment

Positive control(s):

Crystalline silica was examined simulataneously.

Examinations

Tissues and cell types examined:

The testing programme included cellular and biochemical Bronchoalveolar Lavage Fluid Analysis (BLA) on inflammatory markers, histopathology, inflammatory cytokine gene expression, immunohistochemisty for DNA damage, and mutagenesis in alveolar epithelial cells. 

Evaluation criteria:

not specified

Statistics:

Analysis of variance, Dunnett´s test for determination of differences between control and treated groups.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Remarks:

Alveolar type-II cells isolated from the 50-mg/m3 rat group showed no increased mutation frequency as compared to the control.

Toxicity:

no effects

Remarks:

Viability in lung-cell isolates was not impaired (see Report p. 409).

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

No differences were detected between treatment groups in the yield of alveolar type-II cells or the viability of lung-cell isolates.

There was no increase in 6TG-resistant mutants (av. approx. 4 mutants/10^6 cells vs. control (7.6 +-3.4 mutants/10^6 cells in the air control) immediately after exposure of rats to 50 mg/m3 of amorphous silica, whereas after exposure to crystalline silica(3 mg/m3), the mutant frequency was significantly enhanced (approx. 33 mutants/10^6 cells) despite the more than 10-fold lower exposure concentration (Report Fig. 4).
  

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative