Fumes, silica

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1974

Report date:

1974

Materials and methods

Test guideline

Test guideline 1

Qualifier:

no guideline available

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Deviations:

yes

Remarks:

without external metabolic activation system

Principles of method if other than guideline:

Method: Culture technique, determination of cytotoxicity and test for chromosomal aberrations decribed and similar to current guideline (OECD 473)

GLP compliance:

no

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

112926-00-8

EC Number:

601-214-2

Cas Number:

112926-00-8

IUPAC Name:

112926-00-8

Details on test material:

Syloid 244 (named FDA 71-48): CAS-Name: Silica gel, cryst.-free; CAS-No. 112926-00-8

Method

Species / strain

Species / strain / cell type:

other: Human embryonic lung cells (WI-38)

Metabolic activation:

without

Test concentrations with justification for top dose:

0.1, 1.0, and 10 µg/ml (note: mcg/ml is stated: Tab. Test I, p. 83)
Dose selection: 10 µg/ml was the highest level free of observable cell clumping (see Report p. 6/7).

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: water, 0.85 % saline
- Justification for choice of solvent/vehicle: suspension

Controls

Negative solvent / vehicle controls:

yes

Remarks:

saline

Positive controls:

yes

Positive control substance:

triethylenemelamine

Remarks:

Migrated to IUCLID6: 0.1 µg/ml

Details on test system and experimental conditions:

METHOD OF APPLICATION: in suspension, 5 x10^5 cells/mL
Mutations were quantified by counting anaphase aberrations.

DURATION
- Incubation temperature: 37 °C
- Exposure duration: 24 - 48 h

Fixation: absolute methanol:glacial acetic acid (3:1) for 30 min after centrifugation
STAIN (for cytogenetic assays): acetic acid-orcein stain (2.0 %)

NUMBER OF REPLICATIONS: 3/dose level

NUMBER OF CELLS EVALUATED: 100/dose level

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; other: "any cytopathic effect" at 24, 48, and 72 h after exposure to dose levels logarithmatically spaced


OTHER EXAMINATIONS:
- Determination of polyploidy: yes

Results and discussion

Test results

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Remarks:

"clumping" of cells as criterion for maximum dose selection

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

other: other: Human embryonic lung cells (Wi-38)

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Anaphase aberrations (from Report Table p. 83)

	Mitotic index^1)	No. of cells	% cells with acentric frag.	% cells with bridges	% multipolar cells	% cells other aberr.^2)	% cells with aberr.
Syloid
0.1 µg/mL	3	100	3	0	0	0	3
1.0 µg/mL	4	100	4	1	0	0	5
10.0 µg/mL	4	100	0	0	0	0	0
Saline	3	100	1	0	0	0	1
TEM (0.1 µg/mL)	2	100	13	4	1	3 (pp)	21

¹⁾ % cells in mitosis: 200 cells observed/dose level

²⁾ Cells with polyploidy, pulverisation (pp), or greater than 10 aberrations

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative