Germanium dioxide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Remarks:

Test according to state-of-the-art operating procedures for testing of metal bioelution.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Objective of study:

bioaccessibility (or bioavailability)

Test guideline

Qualifier:

according to guideline

Guideline:

other: ASTM D5517-07: Standard Test Method for determining the extractability of metals from art materials - ASTM, 2007 (American Society for Testing and Materials).

Principles of method if other than guideline:

The release/dissolution of germanium from germanium(IV) oxide in simulated gastric fluid was measured. The resulting value is termed bio-accessibility, and is defined as the fraction of a substance that is soluble under physiological conditions and therefore potentially available for absorption into systemic circulation. The simulated gastric fluid represents an exposure-relevant exposure route (oral exposure). The compound was introduced as powder in a test item / solution ratio of 200 mg/L during 2 hours.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Germanium dioxide

EC Number:

215-180-8

EC Name:

Germanium dioxide

Cas Number:

1310-53-8

Molecular formula:

GeO2

IUPAC Name:

Germanium dioxide

Test material form:

solid: particulate/powder

Details on test material:

Batch number: 968
Description: White Solid (powder)
Purity: 99.9%
Storage conditions: Controlled room temperature (15-25°C, below 70% RH%)
Safety precautions: Routine safety precautions (lab coat, gloves, safety glasses and face mask) for unknown materials were applied to assure personnel health and safety."
Grain size: d50: 14.3 µm
Bulk density: 0.9-1.2 kg/l
Moisture: ≤ 0.5%
Chlorine (Cl): 118 ppm
Aluminium (Al): <0.2 ppm
Calcium (Ca) <0.2 ppm
Iron (Fe) <0.2 ppm
Silicon (Si) <1ppm
solubility >4.5g/l

Results and discussion

Preliminary studies:

not applicable

Main ADME results

Main ADME results 1

Type:

other: bioaccessibility

Results:

gastric fluid (0hours): as %Ge released of total Ge content: 0.09

Main ADME results 2

Type:

other: bioaccessibility

Results:

gastric fluid (1hours): as %Ge released of total Ge content: 10.5

Main ADME results 3

Type:

other: bioaccessibility

Results:

gastric fluid (2hours): as %Ge released of total Ge content: 23.3

Toxicokinetic / pharmacokinetic studies

Details on absorption:

not applicable

Details on distribution in tissues:

not applicable

Details on excretion:

not applicable

Metabolite characterisation studies

Metabolites identified:

not measured

Details on metabolites:

not applicable

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

gastric fluid (0hours): as %Ge released of total Ge content: 0.09
gastric fluid (1hours): as %Ge released of total Ge content: 10.5
gastric fluid (2hours): as %Ge released of total Ge content: 23.3

Any other information on results incl. tables

Germanium dioxide, loading 0.2 g/L (= 5.90 m²/L surface loading)
		2-h gastric at pH 1.2
Analyte		xavg± sbetween	CV
germanium (Ge)	dissolution	32.3 ±1.3 mg/L	4%
	absolute Ge release	162 ± 7 mg/g	4%
	% of total availableGeeluted	23.3%
	Ge release/surface	27.4 mg/m²

x_avg= average of 3 test vessels (blank corrected, if theblankvalue is > reporting limit, otherwise blank assumed as 0)

s_between= standard deviation

CV= Coefficient of Variation (%)

Applicant's summary and conclusion

Conclusions:

The dissolution in gastric fluid is used to estimate bioavailability after oral exposure. Bio-elution test according to state-of-the-art procedures, useful for determining dissolution capacity of In in gastric fluid.
Interpretation of results: low bioaccessibility of Ge from germanium(III) oxide.

Executive summary:

During this study on Germanium dioxide at a loading of 0.2 g/L in simulated gastric fluid (pH 1.2), it was shown that a significant amount of germanium (average dissolved germanium concentration of 32.3 ± 1.3 mg/L Ge or 162mg/g Ge with a between-vessel variation of 4% (CV=4%)) was measured after 2 hours of extraction. Based on the specific surface area of Germanium dioxide (i.e. 5.90 m²/g test item), a germanium release per surface 27.4 mg/m² was calculated. Based on the germanium content in the test item (69.4%) and the average dissolved germanium concentration, a germanium release of 23.3% could be calculated.