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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
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, based on scientific standards, documentation limited, acceptable for assessment
Cross-reference
Reason / purpose:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1956
Report Date:
1956
Reference Type:
other company data
Title:
Unnamed
Year:
1953
Report Date:
1953

Materials and methods

Objective of study:
distribution
Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: OECD Guideline 452 (Chronic Toxicity Studies), oral feed, 24 months
Principles of method if other than guideline:
Determination of Si levels in various organs at termination of a chronic feeding study.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Silene EF
- Substance type: inorganic
- Physical state: solid; white powder
- Analytical purity:
- Impurities (identity and concentrations):
- Composition of test material, percentage of components: SiO2 (64 %); CaO (18 %); Al2O3 (0.6 %); MgO (0.1 %); NaCl (1.5 %) (after ingnition)
- loss at 105 °C: 5 %
- loss on ignition: 15 %
- pH ~10 (5 % water suspension)
- surface area: 80 m2/g
- Lot/batch No.:
Radiolabelling:
no

Test animals

Species:
rat
Strain:
other: albino (Carworth Farm strain)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation: weanling
- Weight at study initiation: averages 70 - 73 g (m, f)
- Fasting period before study: no
- Housing: individual
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS: no data

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: gelatin (15 g/100 mL water)
Details on exposure:
DIET PREPARATION
- Rate of preparation of diet (frequency): weekly
- Particular measures: Based on results from the pre-test, the test compound had be administered in moist form
in order to suppress its alkalinity and dustability.
- Mixing appropriate amounts: Appropriate amounts of the Silene-gelatine mixtures were mixed
with the basic diet in a twin-shell blender on w/w basis.
The amount of gelatine added to all diets including controls remained constant
throughout the whole experiment.

- Storage temperature of food: no data

- Dosage regimen: The high-dose groups had accustom to the diet containing higher levels of Silene:
Therefore, gradual increase in Silene content:
7.5% group: increase from 5 to 7.5 % after 3 wks;
10% group: increase from 5 to 7.5 % after 3 wks, further increase from 7,5 to 10 % after 10 wks.



VEHICLE
- Justification for use and choice of vehicle (if other than water):
Based on results from the pre-test, the test compound had be administered in moist form
in order to suppress its alkalinity and dustability.
- Concentration in vehicle: variable, depending on the dose


HOMOGENEITY AND STABILITY OF TEST MATERIAL: no data
Duration and frequency of treatment / exposure:
24 months
Doses / concentrations
Remarks:
Doses / Concentrations:
1.0, 5.0, 7.5, and 10 % (w/w) in feed, 7.5 and 10 % after an acclimation period to higher levels (see "Diet Preparation" above)
No. of animals per sex per dose:
6 m and 6 f of each dose level, tissues of 3 animals of each sex pooled for analysis (2 replicates).
Control animals:
yes, concurrent vehicle
Positive control:
none
Details on dosing and sampling:
ANALYSIS of TISSUE Sections (see Report, Table 52)
- silicon dioxide content: upon termination of the experiment:
in kidney, liver, spleen, cardiac muscle, skeletal muscle, and testes:
from 6 m and 6 f of each dose level, tissues of 3 animals of each sex pooled for analysis (2 replicates)

(Method of analysis according to King and Stential: outlined in an interim report that is not available.)

Statistics:
no data, arithmetic means +_S.D.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
no data available
Details on distribution in tissues:

After 104 weeks, there was a dose-related increase of Si in the kidney and liver, but not in the other organs examined:
The increase was more marked in males than in females, and much higher in the kidney than in the liver.

Kidney at 5 % level: approx. 3x background (m), no or only slight increase (f)
at 10 % level: approx. 20x background (m), approx. 15x background (f)

Liver at 5 % level: approx. 2x background (m), no or only slight increase (f)
at 10 % level: approx. 3x background (m), approx. 3x background (f)

No time-related organ levels other than 104 weeks have been investigated.
Details on excretion:
no data available

Metabolite characterisation studies

Details on metabolites:
not applicable

Any other information on results incl. tables

Si level in kidneys and livers of rats receiving calcium silicate (Silene EF) in the feed for 104 weeks

(Data adopted from Report, Table 52)

 

Level in diet [%]

Males

Females

Si as SiO2[mg/100 g tissue]

Si as SiO2[mg/100 g tissue]

Kidney

Liver

Kidney

Liver

Sample*)

average

Sample*)

average

Sample*)

average

Sample*)

average

Control

2.26
0.83

1.54

0.83
1.39

1.11

0.98
2.41

1.69

0.58
1.23

0.91

1.0

2.60
3.49

3.05

0.86
1,10

0.98

2.24
2.29

2.27

2.04
0.49

1.27

5.0

5.45
4.88

5.17

2.96
2.04

2.50

2.79
1.61

2.20

1.37
1.54

1.45

7.5

14.8
11.9

13.35

2.03
2.05

2.04

13.2
7.97

10.58

1.98
3.00

2.49

10.0

41.4
32.4

36.90

3.11
4.07

3.59

24.7
22.7

23.70

3.30
3.22

3.26

*) Sample n = 3 each

No significant differences from the controls can be concluded from Si levels in spleen, heart, skeletal muscle,

and testes (Data from the report not shown).

Applicant's summary and conclusion