Ashes (residues), rice husk

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: 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

Test material information

Constituent 1

Reference substance name:

Cristobalite

EC Number:

238-455-4

EC Name:

Cristobalite

Cas Number:

14464-46-1

IUPAC Name:

14464-46-1

Details on test material:

- Name of test material (as cited in study report): Cristobalite, crystalline 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:
3 ± 1 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:

positive

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. Exposure to 3 mg/m3 crystalline silica resulted in HPRT mutation frequencies which were 4.3 -fold greater than the air control group, immediately after 13 weeks of exposure.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): positive