Registration Dossier

Toxicological information

Basic toxicokinetics

Currently viewing:

Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
January to March 2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Meets generally accepted scientific standards, well documented and acceptable for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Objective of study:
other: Leaching of Tungsten dioxide in syntethic biological fluids (termed bioaccessibility).
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
This report measured bioaccessibility of Tungsten dioxide in body fluid simulants as a surrogate for bioavailability.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Tungsten dioxide
- Substance type: inorganic
- Physical state: solid
Radiolabelling:
no

Test animals

Species:
other: not applicable
Strain:
other: not applicable
Details on test animals and environmental conditions:
Not applicable

Administration / exposure

Route of administration:
other: In vitro study
Vehicle:
other: not applicable
Details on exposure:
Not applicable
Duration and frequency of treatment / exposure:
Not applicable
Doses / concentrations
Remarks:
Doses / Concentrations:
0.1 g of test substance in 50 mL of simulated fluid
No. of animals per sex per dose:
Not applicable
Control animals:
other: not applicable
Positive control:
Not applicable
Details on study design:
Tungsten dioxide was extracted in leaching fluids for different time periods: 5hrs in simulated gastric fluid, 2 and 24 hrs in simulated interstitial and lysosomal solution and 12 hrs in artificial perspiration. The extractions were performed using 0.1 gram of sample in 50 ml of simulated fluid. A shaker water bath at a temperature of 37°C was used. All extractions were performed in triplicate. The extracts were analyzed for soluble tungsten using EPA Method #200.7 (ICP). Results were reported as ug W/g sample, % W/g sample and as % of total available W released.
Details on dosing and sampling:
Not applicable
Statistics:
Not applicable

Results and discussion

Preliminary studies:
Not applicable

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

Any other information on results incl. tables

Table 1: Soluble Tungsten in gastric fluid

Extraction time in h

Weight used (g)

µg Tungsten/g Sample

% Tungsten release/Tungsten content

5

0.1003

1,994

0.23

(dup)

0.1034

1,886

0.22

(trip)

0.1048

2,052

0.24

 

Table 2: Soluble Tungsten in simulated interstitial fluid

Extraction time in h

Weight used (g)

µg Tungsten/g Sample

% Tungsten release/Tungsten content

2

0.1010

3,218

0.38

(dup)

0.1006

3,181

0.37

(trip)

0.1015

2,956

0.35

24

0.1039

7,267

0.85

(dup)

0.1046

6,597

0.77

(trip)

0.1036

6,226

0.73

 

Table 3: Soluble Tungsten in lysosomal fluid

Extraction time in h

Weight used (g)

µg Tungsten/g Sample

% Tungsten release/Tungsten content

2

0.1013

4,393

0.52

(dup)

0.1003

4,487

0.53

(trip)

0.1019

4,612

0.54

24

0.1024

29,150

3.42

(dup)

0.1008

26,835

3.15

(trip)

0.1026

28,606

3.36

 

Table 4: Soluble Tungsten in artificial perspiration

Extraction time in h

Weight used (g)

µg Tungsten/g Sample

% Tungsten release/Tungsten content

12

0.1028

38,473

4.52

(dup)

0.1017

39,381

4.62

(trip)

0.1036

37,645

4.42

 

 

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results Data for read-across assessments for tungsten dioxide
Based on the results, the bioavailability of Tungsten dioxide would be expected to be low for all routes of administration and best at slightly acidic to neutral pH.
Executive summary:

This report measured bioaccessibility of Tungsten dioxide as a surrogate for bioavailability. To do this the soluble Tungsten was measured using the EPA method #200.7 (ICP) after incubation of Tungsten dioxide in simulated body fluids (simulated gastric fluid, simulated interstitial fluid, simulated lysosomal fluid, and artifical perspiration). Results were reported as ug W/g sample, % W/g sample and as % of total available W released.

Overview of W released in the different simulated body fluids:

Medium

T in h

% W-release from WO2

Simulated gastric fluid

5

0,23 %

Simulated interstitial fluid

2

0,37 %

24

0,78 %

Simulated lysosomal fluid

2

0,53 %

24

3,31 %

Artifical perspiration

12

4,52%

 

In summary, release of Tungsten from WO2 was best in simulated lysosomal fluid and artificial perspiration. The bioavailability in the fluids ranged from 0,23 % (simulated gastric fluid) to 4,52 % (artificial perspiration). Thus, the maximum solubility was measured in artificial perspiration. Based on the results, the bioavailability of Tungsten dioxide would be expected to be low for all routes of administration and best at slightly acidic to neutral pH.