Tungsten oxide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2009-01-28 to 2009-05-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The bioaccessability study described in this report was performed according to the "Draft Guidance for RIP 3.6: Bioavailability and Read-Across for Metals and Minerals". GLP study.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Objective of study:

absorption

Test guideline

Qualifier:

according to guideline

Guideline:

other: Draft Guidance for RIP 3.6: Bioavailability and Read-Across for Metals and Minerals

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tungsten oxide

EC Number:

254-413-8

EC Name:

Tungsten oxide

Cas Number:

39318-18-8

Molecular formula:

WOn (n=2.99 to 2.90)

IUPAC Name:

tungsten(6+) trioxidandiide

Details on test material:

- Name of test material (as cited in study report): Tungsten Blue Oxide
- Substance type: Pure active substance
- Physical state: Solid
- Lot/batch No.: BV/2181
- Impurities (identity and concentrations): <2 ppm Al, <2 ppm Ca, <5 ppm Co, <5 ppm Cr, <5 ppm Fe, <4 ppm K, <10 ppm Mo, 2 ppm Na, <5 ppm Ni, <5 ppm S, <10 ppmSi
- Purity test date: 2008-04-29

Radiolabelling:

no

Test animals

Species:

other: Human simulated fluids

Strain:

not specified

Sex:

not specified

Administration / exposure

Route of administration:

other: In vitro study

Vehicle:

other: Not applicable

Details on exposure:

Preparation of Testing Fluids: The simulated fluids used in this study were gastric, lung alveolar, lung interstitial, lysosomal and artificial sweat. All salts and reagents used for the simulated fluid preparation were obtained from Sigma-Aldrich (St. Louis, MO).

Extraction Experiments: Extractions of the test substances in the simulated fluids were performed at pre-set time periods (up to 72 hours) while protected from light, using 0.1 g of sample in 50 ml of simulated fluid, at 37 °C and with continuous shaking (for all fluids except sweat, for which only initial shaking was performed). The experiments were carried out as follows:
- Simulated Gastric Fluid: The reactions were sampled for the determination of tungsten at 5 hours.
- Simulated Interstitial, Alveolar and Lysosomal Fluids: 5% CO2 in nitrogen was bubbled into solution at a rate of 50 ml/min. The reactions were sampled for the determination of tungsten at 2, 5, 24 and 72 hours.
- Simulated Sweat: The reactions were sampled for the determination of tungsten after 12 hours. No shaking was performed after the initial set up.

Sample Preparation: The simulated fluid extract samples were filtered immediately after sampling using 50 ml centrifuge tubes equipped with 0.45 microns PVDF filters (Grace Alltech, Deerfield, IL). The filtrates were stored in plastic bottles at 35 °C until analysis.

The extracts were then analyzed for tungsten by inductively coupled plasma-mass spectrometry (ICP-MS).

Duration and frequency of treatment / exposure:

Single application of tungsten with fluids. Simulated Gastric Fluid was sampled for the determination of tungsten at 5 hours. Simulated Interstitial, Alveolar and Lysosomal Fluids were sampled for the determination of tungsten at 2, 5, 24 and 72 hours. Simulated Sweat was sampled for the determination of tungsten after 12 hours.

Doses / concentrations

Remarks:

Doses / Concentrations:
0.1 g of test substance in 50 mL of simulated fluid

Control animals:

no

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: Simulated gastric fluid, Simulated interstititial fluid, Simulated alveolar fluid, Simulated lysosomal fluid and Simulated sweat
- Time and frequency of sampling: Simulated gastric fluid sampled at 5 hours, Simulated interstititial fluid sampled at 2, 5, 24 and 72 hours, Simulated alveolar fluid sampled at 2, 5, 24 and 72 hours, Simulated lysosomal fluid sampled at 2, 5, 24 and 72 hours and Simulated sweat sampled after 12 hours.

Sample analysis: Samples were diluted (if necessary), spiked with an internal standard [bismuth (Bi) at 1,000 pg/mL, prepared from dilution of a 1,000 ug/mL Certified Standard; Ultra Scientific, North Kingston, RI and analyzed directly on a Perkin Elmer Elan DRC II ICP-MS equipped with a dynamic reaction cell (DRC) and PerkinElmer AS-93 Plus autosampler instrument, according to methods established at IITRI for this study. A standard curve (prepared from dilutions of a 10,000 5%HNO3/6% HF; inorganic Ventures, Lakewood, NJ was analyzed along with samples on each day of analysis. Instrument calibrators were prepared by diluting Certified Standard with 0.5% nitric acid to concentrations of approximately 200; 400; 800; 1,600; 3,200; 6,400; 13,000 and 25,000 pg/mL.

Statistics:

Calibration curves, regression coefficients and r-squared values were calculated using PerkinElmer ICP-MS software and Microsoft Excel software. Concentration values of tungsten in the study samples were calculated from linear regression coefficients derived from calibration standards that bracketed the expected concentration levels of tungsten in the study samples.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Transfer into organs

Transfer type:

other: Not applicable since this was an in vitro study

Toxicokinetic parameters

Toxicokinetic parameters:

other: not applicable since this was an in vitro study

Metabolite characterisation studies

Metabolites identified:

not measured

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

The fluid extracts were diluted 1:500 to 1:125000 for analysis. The average amount of tungsten found in the extracts was in the 0.0767 to 60% range. The maximum solubility was determined at 72 hours for the simulated alveolar, lysosomal and interstitial fluids (41, 60 and 40%, respectively). % RSDs ranged from 0.81 to 71%.
Gastric Fluid: The percent of available tungsten in simulated gastric fluid sampled at 5 hours was 0.0767 +/- 0.0014 % (1.8 % relative standard deviation).
Sweat Fluid: The percent of available tungsten in simulated sweat fluid sampled at 12 hours was 7.7 +/- 0.31 % (4.1 % relative standard deviation).
Alveolar Fluid: The percent of available tungsten in simulated alveolar fluid sampled at 2, 5, 24 and 72 hours was 1.02 +/- 0.0116%, 4.6 +/- 3.3%, 39 +/- 5.2% and 41 +/- 5.4 %, respectively, with percent relative standard deviations of 1.1, 71, 13 and 13 % RSD, respectively.
Lysosomal Fluid: The percent of available tungsten in simulated lysosomal fluid sampled at 2, 5, 24 and 72 hours was 0.90 +/- 0.049, 2.4 +/- 0.019, 35 +/- 1.7 and 60 +/- 5.8 %, respectively, with percent relative standard deviations of 5.4, 0.81, 4.7 and 9.6 % RSD, respectively.
Interstitial Fluid: The percent of available tungsten in simulated interstitial fluid sampled at 2, 5, 24 and 72 hours was 2.1 +/- 0.12%, 3.6 +/- 0.26%, 23 +/- 8.9% and 40 +/- 0.59 %, respectively; with percent relative standard deviations of 5.5, 7.3, 39 and 1.5 % RSD, respectively.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
The average amount of tungsten found in the extracts was in the 0.0767 to 60% range. The maximum solubility was determined at 72 hours for the simulated alveolar, lysosomal and interstitial fluids (41, 60 and 40%, respectively). % RSDs ranged from 0.81 to 71%.
In the simulated gastric fluid the percent of available tungsten sampled at 5 hours was 0.0767 +/- 0.0014 % (1.8 % relative standard deviation). In the simulated sweat fluid the percent of available tungsten sampled at 12 hours was 7.7 +/- 0.31 % (4.1 % relative standard deviation). In the simulated alveolar fluid the percent of available tungsten sampled at 2, 5, 24, and 72 hours was 1.02 +/- 0.0116%, 4.6 +/- 3.3%, 39 +/- 5.2% and 41 +/- 5.4 %, respectively, with percent relative standard deviations of 1.1, 71, 13 and 13 % RSD, respectively. In the simulated lysosomal fluid the percent of available tungsten sampled at 2, 5, 24 and 72 hours was 0.90 +/- 0.049, 2.4 +/- 0.019, 35 +/- 1.7 and 60 +/- 5.8 %, respectively, with percent relative standard deviations of 5.4, 0.81, 4.7 and 9.6 % RSD, respectively. In the simulated interstitial fluid the percent of available tungsten sampled at 2, 5, 24 and 72 hours was 2.1 +/- 0.12%, 3.6 +/- 0.26%, 23 +/- 8.9% and 40 +/- 0.59 %, respectively; with percent relative standard deviations of 5.5, 7.3, 39 and 1.5 %RSD, respectively.