Tungsten dioxide

Basic toxicokinetics

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

Test material information

Constituent 1

Reference substance name:

Tungsten dioxide

EC Number:

234-842-7

EC Name:

Tungsten dioxide

Cas Number:

12036-22-5

Molecular formula:

O2W

IUPAC Name:

dioxotungsten

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 or test system 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 / concentration:

Not applicable

Control animals:

other: not applicable

Positive control reference chemical:

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.