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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: Basic data given, meets generally accepted scientific standards, acceptable for assessment

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1966
Report Date:
1966
Reference Type:
publication
Title:
No information
Author:
Langendorf H, Lang K
Year:
1967
Bibliographic source:
Zeitschrift fuer Ernaehrungswissenschaft, 8, 27-32

Materials and methods

Objective of study:
excretion
Principles of method if other than guideline:
Study in volunteers: Oral ingestion of an SAS amount in a drink, determination of Si in urine prior and after to administration.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Aerosil, CAS-Name: Silica, amorphous, fumed, cryst.-free; CAS-No. 112945-52-5

FK 700, Silica, amorphous, precipitated, crystalline-free, CAS No. 112926-00-8
Radiolabelling:
no

Test animals

Species:
human
Sex:
male/female

Administration / exposure

Route of administration:
other: oral in juice
Vehicle:
other: apple juice, 0.5% suspension
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:

DIET PREPARATION
- Mixing appropriate amounts with (Type of food): 2.5 g of test substance in 0.5 L (apple juice)

VEHICLE
- Concentration in vehicle: 0.5 %
- Amount of vehicle (if gavage): 0.5 L


HOMOGENEITY:
Suspension
Duration and frequency of treatment / exposure:
1x/day, given in two portions (see below)
Doses / concentrations
Remarks:
Doses / Concentrations:
Males: 2x 1250 mg (morning and midday) Females: 2x 1250 mg (morning and midday)
No. of animals per sex per dose:
Males: 10; Females: 2 (age 22 - 28 years)
(for each test article: 5 m+ 1 f )
Control animals:
other: untreated control = each volunteer before silica intake
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine
- Time and frequency of sampling: for 3 days pre-application and for 4 days post-application, total daily urine

- Method type(s) for identification: SiO2 determination according to Baumann (after alkaline hydrolysis with molybdate)
- Limits of detection and quantification: no data

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
no data
Details on distribution in tissues:
no data
Details on excretion:
see below "Remarks on results.."
Toxicokinetic parametersopen allclose all
Test no.:
#1
Toxicokinetic parameters:
other: Aerosil - urinary excretion: <0.5 % of the dose applied within 4 days p.a.
Test no.:
#2
Toxicokinetic parameters:
other: FK 700 - urinary excretion: <0.5 % of the dose applied within 4 days p.a.

Metabolite characterisation studies

Details on metabolites:
not applicable

Any other information on results incl. tables

Daily urinary excretion of SiO2 in volunteers before and after ingestion of synthetic amorphous silica 

Aerosil (pyrogene)

Test person

1

2

3

10

11

12

Sum SiO2 day 1 – 3 [mg/d] (control)

34.5

86.9

62.8

40.4

25.3

36.2

Sum SiO2 day 4 – 7 [mg/d]
(test phase)

32.3

64.5

61.3

60.8

44.5

52.9

            FK 700 (precipitated)    

Test person

4

5

6

7

8

9

Sum SiO2
day 1 – 3 [mg/d] (control)

42.4

36.8

71.4

16.1

39.9

27.4

Sum SiO2
day 4 – 7 [mg/d]
(test phase)

52.2

57.0

81.4

20.4

58.3

21.8

During the four days post-treatment, significant changes of the renal SiO2 excretion were not seen.

Daily SiO2 increments in urine after ingestion ranged between individually 7 and 23 mg, but were barely distiguishable

from the baseline level.

Aerosil:
The individual baseline values of the pretest phase were very variable and individually different, mean excretion rates ranging from 

25 to 87 mg/d. In the post-treatment phase, individual mean excretion rates ranged from 32 to 61 mg/d. 

FK 700: 
The individual baseline values of the pretest phase were very variable and individually different, mean excretion rates ranging 

from 16 to 71  mg/d. 

In the post-treatment phase, individual mean excretion rates ranged from 20 to 81 mg/d. 
   ---------------

Overall, increases in excretion of SiO2 after oral ingestion were not unequivocally detectable. 

The small apparent increases on the average of less than 0.5 % of the total dose were in marked contrast to the high dose of 2500 mg SiO2 applied.  

   --------------------------

Applicant's summary and conclusion