Tungsten disulphide

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:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Objective of study:

bioaccessibility (or bioavailability)

Test guideline

Qualifier:

according to guideline

Guideline:

other: Standard Operating Procedure (SOP) for Bioelution Testing of Metals, Inorganic Metal Compounds, and Metal-Containing Complex Materials: Simulated Gastric Fluid (Eurometaux, July 2016)

Version / remarks:

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

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Tungsten

EC Number:

231-143-9

EC Name:

Tungsten

Cas Number:

7440-33-7

Molecular formula:

W

IUPAC Name:

tungsten

Constituent 2

Reference substance name:

Sulfur

EC Number:

231-722-6

EC Name:

Sulfur

Cas Number:

7704-34-9

Molecular formula:

S

IUPAC Name:

sulfur

Test material form:

solid: particulate/powder

Details on test material:

- Particle size distribution: D50= 3.1 um; D90=6.5 um
- Mass median aerodynamic diameter (MMAD):
- Density: 7.69 g/cm3

Administration / exposure

Doses / concentrations

Dose / conc.:

200 ppm (analytical)

Remarks:

Loading 0.2 g/L

Positive control reference chemical:

Not applicable

Details on study design:

Test conditions:
- Temperature controlled at 37 °C ± 1 °C, in the dark,
- pH initially set at pH 1.5 ± 0.1,
- Agitation speed 100 rpm in a temperature controlled orbital laboratory shaker (orbital size: 1 inch, 2.54 cm).

Performance:
One borosilicate Erlenmeyer flask of 250 mL was used for the blank control vessel without test item. In the test vessels, 10 mg test item were weighed in triplicate into three separate 250 mL Erlenmeyer flasks. A fourth replica with test item (named replica X) was prepared only for the measurement of the initial pH (at the start of the test). This additional test vessel was set up to avoid cross contaminations and did not have further utility in the test. 50 mL of extraction fluid (at 37 °C ± 1 °C) was added to the blank control vessel and each test item vessel. After covering the vessels with a screwcap and swirling the flasks to mix the test item and the medium, the flasks were placed into a thermostatic orbital shaker (37 °C ± 1 °C) at an agitation rate of 100 revolutions per minute for one hour. After that, the flasks were settled at 37 °C ± 1 °C for another hour.

Details on dosing and sampling:

At the end of the incubation period (2 hours = 1 hour shaking at 100 rpm and 1 hour settling), each vessel was swirled to homogenise the solution prior to sampling, in order to avoid a concentration gradient after settling.

Sampling was performed for the blank control and each test item vessel as indicated in the sampling scheme below. In each test vessel, a 12-mL sample was taken twice with a 12 mL syringe from the test vessel at a depth of two-thirds of the supernatant. The samples were filtrated through a 0.2 µm syringe filter and transferred to uniquely labelled 15-mL PP sample tubes. The samples were preserved by adding 0.12 mL concentrated HNO3 per 12 mL. The samples were covered (to avoid evaporation and concentration) and stored at room temperature in the dark..

The determination of dissolved tungsten concentrations in the blank control and test item vessels were carried out using an ICP-MS

Statistics:

The data from the analytical laboratory are expressed in µg element per L solution. These data are recalculated (blank corrected and taken into account the actual weighed amount of test item) and expressed in µg element per g test item and as percent metal release of the total available element.

The results are also expressed as released element per surface (mg/m²), based on the results of the N-BET analyses. The dataset of n vessels were analysed. The between-vessel mean, standard deviation, and coefficient of variation of the measured dissolved element concentrations.

A between-vessel coefficient of variation of <20% are quality criteria for the 2 hours endpoint. With very low concentrations close to the detection limit of the analytical method, such as may be with blanks or with a substance that releases element concentrations close to the detection limit, the betweenvessel coefficient of variation can be expected to exceed this target coefficient of variation. Moreover, should the substance be characterised by a wide particle size range, the possibility exists that this coefficient of variation target may not be readily met

Results and discussion

Metabolite characterisation studies

Metabolites identified:

no

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

he following observations could be made in the test vessels with a loading of 0.2 g/L Tungsten Disulphide:
- A silvery shining layer of particles covered the surface of the test fluid. Remaining test item (grey particles) could be observed at the bottom of the Erlenmeyer flasks at the end of the experiment. The test solutions were colourless. A slight smell of H2S could be observed.

- An average dissolved tungsten concentration of 98.4 ± 1.0 µg/L W (or 491 ± 5 µg/g test item) was measured after 2 hours of exposure to the simulated gastric fluid (pH 1.5) with a between-vessel variation of 1 % which meets the 20 % quality criterion at the 2 hours endpoint.

- Based on the specific surface area of Tungsten Disulphide (2.70 m²/g test item) a tungsten release per surface of 0.18 mg/m² was calculated.
- Based on the tungsten content of the test item (i.e. 74.0 %) and the average dissolved tungsten concentration, a tungsten release of 0.066 % could be calculated at the 2 hours endpoint.

Any other information on results incl. tables

The temperature of the test solutions at the sampling point was between 36.9 °C and 37.1 °C, which was in line with the test conditions of 37 °C ± 1 °C. The measured pH of the test medium at the start of the test was 1.50, i.e. within the specifications of pH 1.5 ± 0.1. The pH measured in the additional test item vessel at the start of the test was 1.50 i.e. within the specifications of pH 1.5 ± 0.1. At the 2 hours sampling point of the test, the pH in the blank control vessels and the test vessels was between 1.50 and 1.51. The blank control vessel showed no concentrations of tungsten above the reporting limit of 0.5 µg/L W

Applicant's summary and conclusion

Conclusions:

During this study on Tungsten Disulphide at a loading of 0.2 g/L in simulated gastric fluid (pH 1.5), it was shown that for tungsten an average value of 98.4 µg/L W (CV = 1 %) was found after 2 hours of extraction, corresponding with a tungsten release of 0.066 % (or 0.18 mg/m²).

Executive summary:

Bio-elution refers to the in vitro extraction methods used to measure the degree to which a substance (e.g., metal or mineral ion) is dissolved in artificial biological fluids. Simulated biological fluids represent

relevant exposure routes. The resulting value is the “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 objective of this study was to obtain knowledge about the bio-elution characteristics of Tungsten Disulphide in simulated gastric fluid. This study has been conducted according to the recommended Standard Operating Procedure (SOP) for Bioelution Testing of Metals, Inorganic Metal Compounds, and Metal-Containing Complex Materials: Simulated Gastric Fluid (Eurometaux, July 2016) which is based on ASTM D5517-07: Standard Test method for determining the extractability of metals from art materials - ASTM, 2007 (American Society for Testing and Materials). The extent of dissolution of Tungsten Disulphide with a particle size <100 µm was tested in a simulated gastric fluid at 37 °C and pH 1.5 during 2 hours (0.2 g/L loading) at an agitation speed of 100 revolutions per minute (rpm). The bio-elution endpoints were based on the dissolved tungsten (W) concentrations obtained after 2 hours of extraction. The study was performed at ECTX. Analysis of the concentrations of dissolved tungsten has been performed at Waterlaboratorium Noord (WLN) (The Netherlands), an ISO 17025 accredited laboratory, as delegated by ECTX. The measured pH of the test medium at the start of the test was 1.50, i.e. within the specifications of pH 1.5 ± 0.1. The pH measured in the additional test item vessel at the start of the test was 1.50 i.e. within the specifications of pH 1.5 ± 0.1. At the 2 hours sampling point of the test, the pH in the blank control vessels and the test vessels was between 1.50 and 1.51. The temperature of the sampled test solutions including the blank test vessel was between 36.9 °C and 37.1 °C and corresponded to the required test conditions of 37 °C ± 1 °C. The blank control vessels showed no concentrations of tungsten above the reporting limit of 0.5 µg/L W. In the blank corrected test item vessels with a loading of 0.2 g/L Tungsten Disulphide, the following average dissolved tungsten concentration of: 98.4 ± 1.1 µg/L W (CV = 1 %), was measured after 2 hours of exposure to the simulated gastric fluid (pH 1.5).

- Based on the specific surface area of Tungsten Disulphide (i.e. 2.70 m²/g), this corresponds with a tungsten release per surface of: 0.18 mg/m².

- Based on the tungsten content (i.e. 74.0 %) in the test item and the average dissolved tungsten concentrations in the test solutions a tungsten release of: 0.066 %, could be calculated at the 2 hours endpoint.