Kaolin, calcined

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

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 with acceptable restrictions (limited documentation, no data on test substance purity).

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1974

Report date:

1974

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

yes

Remarks:

- only male animals; only three animals in negative control group; only 500 cells evaluated for mitotic index; no bone marrow toxicity in highest concentration used

GLP compliance:

no

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Details on test material:

- Name of test material (as cited in study report): synthetic silica sodium silicoaluminate (FDA 71-45)
- Physical state: fine white powder
- Analytical purity: no data

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 10-12 weeks
- Weight at study initiation: 300 to 350 g
- Housing: Rats were housed one to five per cage.
- Diet (e.g. ad libitum): commercial 4 % fat diet; periodic tests to verify the absence of coliforms, Salmonella and Pseudomonas sp. were performed.
- Water (e.g. ad libitum): water; 2 times per week water was changed
- Quarantine: 4 to 11 days
- Others: Animals were identified by ear punch. Sanitary cages and bedding were changed two times per week.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

saline (0.85 %)

Duration of treatment / exposure:

acute study: single dose (post exposure period: up to 48 hours)
subacute study: five days

Frequency of treatment:

acute study: single dose
subacute study: 5 doses, daily

Post exposure period:

acute study: sampling times 6, 24 and 48 h after administration of test substance
subacute study: animals were sacrificed 6 hours after the last dose

Doses / concentrations

Remarks:

Doses / Concentrations:
acute + subacute: 4.25, 42.5, 425 mg/kg bw
Basis:
nominal conc.

No. of animals per sex per dose:

5; only 3 animals in negative control group
acute study: 59
subacute study: 18

Control animals:

yes, concurrent vehicle

Positive control(s):

0.3 mg/kg triethylene melamine (TEM) administered intraperitoneally

Examinations

Tissues and cell types examined:

freshly isolated bone marrow cells

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION:
The dose of 425 mg/kg corresponds to the LD5.

DETAILS OF SLIDE PREPARATION: Fixed cells were dropped on slides and dried. Slides were stained using a 5% Giemsa solution, subsequently rinsed with acetone/xylene and placed in xylene for 30 min before counting.

METHOD OF ANALYSIS:
Duplicate slides were examined microscopically. Only diploid cells were analyzed.

OTHER: 2 h prior to killing, each animal was given 4 mg/kg of colcemid intraperitoneally.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Remarks:

LD5 = 425 mg/kg

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

The compound produced no detectable significant aberration of the bone marrow metaphase chromosomes of rats when administered orally at the tested dosage levels. The test compound can be considered non-mutagenic.

Any other information on results incl. tables

acute study: The negative controls and the 3 compound-treated groups were within the normal limits of breaks observed (0 -3%). The mitotic indices were in good agreement except for the 425 mg/kg group which was slightly, but not significantly, depressed. In the positive control group 5% of the cells with severe damage (> 10 aberrations/cell) and 1% of the cells with pulverized chromosomes were observed.

Dose [mg/kg]	Sampling time [h]	Mitotic index [%]	Cells with aberrations [%]
0 (saline)	6	10	2
	24	11	3
	48	9	3
4.25	6	11	2
	24	11	1
	48	11	3
42.5	6	8	0
	24	9	1
	48	10	0
425	6	12	2
	24	6	0
	48	10	2
TEM 0.3	48	3	48

subacute study: The negative control groups and the three treated groups were within normal limits for breaks and mitotic indices.

Dose [mg/kg]	Mitotic index [%]	Cells with aberrations [%]
0 (saline)	8	3
4.25	10	2
42.5	11	2
425	8	3

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative