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Toxicological information

Genetic toxicity: in vivo

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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 guidelineopen allclose all
Qualifier:
no guideline available
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

Constituent 1
Chemical structure
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

index1)

% 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
   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

index1)

% 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