Synthetic wollastonite

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:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to 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 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Principles of method if other than guideline:

Analysis of metaphase-chromosomes from isolated bone-marrow cells after colcemid-induced arrest of cell division in the metaphase

GLP compliance:

no

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

Silicic acid, calcium salt

EC Number:

215-710-8

EC Name:

Silicic acid, calcium salt

Cas Number:

1344-95-2

IUPAC Name:

calcium oxosilanediolate

Details on test material:

FDA-Compound 71-41 = Silene, calcium silicate (hydrated)

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: 10 - 12 weeks

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- vehicle: 0.85 % saline
- Volume of the vehicle: no data
- Justification for choice of solvent/vehicle: no data
- Concentration of test material in vehicle: no data


MAXIMUM DOSE VOLUME APPLIED: no data

Details on exposure:

3 time points: sampling at 6, 24, and 48 h in the single-dose study
1 time point: sampling at 6 h after the last dose in the repeated-dose study

Colcemide (4 mg/kg bw i.p) was given 2 h prior to kill.

Duration of treatment / exposure:

single administration ("acute") and repeated administration (5 times, "subacute")

Frequency of treatment:

1x, and 5x(1x/d)

Doses / concentrations

Remarks:

Doses / Concentrations:
acute and subacute: 15, 150, 1500 mg/kg suspended in 0.85 % saline
Basis:

No. of animals per sex per dose:

Single-dose study: 5 per time point and dose = 15 per dose in total; vehicle control: 3 per time point and dose = 9 per dose in total
Repeated-dose study: 5 per dose; vehicle control: 3 per dose (report, p. 124)

Control animals:

yes, concurrent vehicle

Positive control(s):

triethylenemelamine
- Route of administration: i.p.
- Doses / concentrations: 0.3 mg/kg bw

Examinations

Tissues and cell types examined:

bone-marrow cells, diploids
50 metaphase spreads per animal were counted (=> 250 in total per dose and pos. control; 150 in total in the control ).
Mitotic indices based at least on 500 cells: ratio of cells in mitosis/total cell count

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: pre-test on toxicity

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):

DETAILS OF SLIDE PREPARATION: Standard fixation and staining with Giemsa. Duplicate slides were prepared.

METHOD OF ANALYSIS: Light microscopy, only diploid cells analysed and scored for chromosomal aberrations

Statistics:

not required

Results and discussion

Test results

Key result

Sex:

male

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

Metaphase aberrations: single dose (from Report Table p. 73)

Silene Dosage [mg/kg bw]	Time [h]	No. of cells	Mitotic index^1)	% cells with breaks	% cells with reunion	% cells with other aberr.^2)	% cells aberr.
15	6	250	7	0	0	0	0
	24	250	8	1	0	0	1
	48	250	12	2	0	0	2
150	6	250	7	1	0	0	1
	24	250	8	0	0	0	0
	48	250	12	3	0	0	3
1500	6	250	14	0	0	0	0
	24	250	14	3	0	0	3
	48	250	10	2	0	0	2
Saline	6	150	11	0	0	0	0
	24	150	9	3	0	0	3
	48	150	14	2	0	0	2
TEM (0.3)	48	250	4	22	12	6(a)	40

¹⁾% cells in mitosis: 500 cells observed/animal

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

Metaphase aberrations: repeated dose (5x, 1x/d) (from Report Table p. 74)

Silene Dosage [mg/kg bw]	Time after last dose [h]	No. of cells	Mitotic index^1)	% cells with breaks	% cells with reunion	% cells with other aberr.^2)	% cells aberr.
15	6	250	8	0	0	0	0
150	6	250	8	3	0	0	3
1500	6	250	7	0	0	0	0
Saline	6	150	10	2	0	0	2

¹⁾% cells in mitosis: 500 cells observed/animal

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

Applicant's summary and conclusion

Conclusions:

Negative