Niobium

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 Aug 2013 - 18 Dec 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study supporting the assessment on toxicokinetic behaviour of niobium metal.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Objective of study:

bioaccessibility (or bioavailability)

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Series on Testing and Assessment No. 29 (23-Jul-2001): Guidance document on transformation/dissolution of metals and metal compounds in aqueous media

Version / remarks:

2001

Deviations:

yes

Remarks:

artificial sweat solution (ASW) and gastric fluid (GST) used instead of water

GLP compliance:

yes (incl. QA statement)

Remarks:

Ministerium fuer Arbeit, Integration und Soziales des Landes Nordrhein-Westfalen, Germany

Test material

Test material information

Constituent 1

Reference substance name:

Niobium

EC Number:

231-113-5

EC Name:

Niobium

Cas Number:

7440-03-1

Molecular formula:

Nb

IUPAC Name:

Niobium

Constituent 2

Reference substance name:

Niobium Metal (Nb)

IUPAC Name:

Niobium Metal (Nb)

Radiolabelling:

no

Test animals

Species:

other: not applicable

Strain:

other: not applicable

Administration / exposure

Route of administration:

other: not applicable

Vehicle:

other: Artificial sweat solution (ASW) and Artificial gastric fluid (GST) were used as media

Details on exposure:

The objective of the present test was to investigate the dissolution of niobium metal in artificial sweat solution (ASW) and artificial gastric fluid (GST). Thus, each test medium was selected to simulate relevant human-chemical interactions, i.e. contact of a test substance with skin and a substance entering the human body by ingestion. Attention was given to establish conditions similar as for human body regarding pH and temperature.
The dissolved amount of test item was specified by the mass concentration of the substance in the test media under the applied test conditions. The total dissolved amount was determined by measuring the total concentrations of dissolved niobium in solution.
For the experimental setup the test item was weighed into flasks, adjusted to volume with the respective artificial physiological medium (loading of 100 mg/L) and agitated at 100 rpm at 37±2 °C. The test was performed in triplicates and two blanks per media were added. Samples were collected after 2 and 24 h. The total concentrations of niobium of sampled solutions were determined after filtration (0.2 µm, Supor membrane) by inductively-coupled-plasma mass-spectrometry (ICP-MS). Mass balance was based on inductively-coupled-plasma optical emission spectrometry (ICP-OES).
To the residual, undissolved test item in the vessels, 80 mL aqua regia (3:1 mixture of concentrated hydrochloric and nitric acid) were added to the flasks after the test. The filter used for sampling were extensively rinsed with aqua regia. Solutions were sampled after at least 24h and the samples were filtered (0.2 µm polyethersulfon membrane, DIA Nielsen, Dueren, Germany). Nb concentrations were measured in mass balance samples (vessels) for each medium by ICP-OES and the mass balance was calculated. It was observed that aqua regia is not sufficient to dissolve the test item and the recovery for the mass balance is not within 100 ± 15 %. Therefore, an additional measurement of the very low concentrations of solution samples from rinsed syringes was regarded not to be reasonable.

For niobium analysis, a commercially available single element standard was used as standard substance (Nb single element standard, lot no. HC264839, expiry date 2015-06-30, Merck, Darmstadt, Germany). This standard solution was used to prepare appropriate stock solutions and subsequently calibration solutions for measurements.

Duration and frequency of treatment / exposure:

2 and 24 h

Doses / concentrations

Remarks:

Doses / Concentrations:
Each test flask was loaded with 100 mg/L of test item.
It was noticed that no more exact weighing of the test item was possible, despite of the use of a microbalance (Mettler Toledo XP 56). This was due to the fact that the test item consists out of fragmented metal pieces with a diameter/width < 1 mm and a length which does not exceed 2.5 mm.

No. of animals per sex per dose / concentration:

not applicable

Control animals:

other: control blanks were added

Results and discussion

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

ICP-MS measurements:
Under the conditions of the test, the results of the ICP-MS measurements of total dissolved niobium in test item loaded samples were as follows:
sample / mean Nb conc. ± SD [µg/L] for all vessels
ASW 2h (duplicate samples, a and b) / 0.4849 ± 0.0204
ASW 24h (duplicate samples, a and b) / 1.991 ± 0.228
GST 2h (duplicate samples, a and b) / 0.2243 ± 0.0233
GST 24h (duplicate samples, a and b) / 0.6886 ± 0.0643

The niobium concentrations in the control blanks were all below the limit of detection (LOD) and limit of quantification (LOQ). LOD was set at 0.039 µg Nb/L for the ASW medium and 0.0033 µgNb/L for the GST medium. LOQ was set at 0.118 µg Nb/L for the ASW medium and 0.0099 µgNb/L for the GST medium.

ICP-OES measurements:
Recoveries of Nb were below LOD and LOQ in ASW and in GST medium, respectively. This clearly shows, that aqua regia is not sufficient to dissolve the test item.

Any other information on results incl. tables

Nb concentrations in test item loaded samples (1, 2, 3 – triplicate vessels; a, b – duplicate samples):

sample	Nb conc. [µg/L] vessel 1	mean Nb conc. ± SD [µg/L] vessel 1	Nb conc. [µg/L] vessel 2	mean Nb conc. ± SD [µg/L] vessel 2	Nb conc. [µg/L] vessel 3	mean Nb conc. ± SD [µg/L] vessel 3	mean Nb conc. ± SD [µg/L] all vessels
ASW2h a	0.4965	0.5039 ± 0.0106	0.4814	0.4891 ± 0.0109	0.4580	0.4618 ± 0.0055	0.4849 ± 0.0204
ASW2h b	0.5114		0.4968		0.4656
ASW24h a	2.343	2.191 ± 0.215	1.755	1.751 ± 0.004	2.121	2.032 ± 0.126	1.991 ± 0.228
ASW24h b	2.039		1.748		1.943
GST 2h a	0.2143	0.2152 ± 0.0013	0.2064	0.2043 ± 0.0031	0.2580	0.2534 ± 0.0065	0.2243 ± 0.0233
GST 2h b	0.2161		0.2021		0.2488
GST 24h a	0.7306	0.7283 ± 0.0033	0.6124	0.6068 ± 0.0079	0.7466	0.7307 ± 0.0225	0.6886 ± 0.0643
GST 24h b	0.7259		0.6012		0.7148

Nb concentrations in method blanks:

medium & sample time	sample	Nb conc. [µg/L] vessel 1	Nb conc. [µg/L] vessel 2	LOD [µg Nb /L]	LOQ [µg Nb /L]
ASW2h	a	<LOD	<LOD	0.039	0.118
	b	<LOD	<LOD
ASW24h	a	<LOD	<LOD
	b	<LOD	<LOD
GST 2h	a	<LOD	<LOD	0.0033	0.0099
	b	<LOD	<LOD
GST 24h	a	<LOQ (0.006)	<LOD
	b	<LOQ (0.007)	<LOD

Amount of niobium in mass balance samples for each media:

medium	Nb concentration after addition ofaqua regia [µg/L]	loading [mg]	LOQ [µg Nb/L]	LOD [µg Nb/L]
ASW vessel 1	< LOQ (2.94)	100.87	3.10	1.03
ASW vessel 2	< LOQ (1.50)	100.76
ASW vessel 3	< LOQ (2.41)	101.23
GST vessel 1	< LOQ (1.40)	101.08	3.10	1 .03
GST vessel 2	< LOQ (1.37)	101.14
GST vessel 3	< LOD	101.05

Applicant's summary and conclusion

Conclusions:

Niobium was neither soluble in artificial sweat solution (ASW) nor in artificial gastric fluid (GST). The objective of the present test was to investigate the dissolution of niobium metal in artificial sweat solution (ASW) and artificial gastric fluid (GST). Thus, each test medium was selected to simulate relevant human-chemical interactions (as far as practical), i.e. contact of a test substance with skin and a substance entering the human body by ingestion. Niobium was neither soluble in artificial sweat solution (ASW) nor in artificial gastric fluid (GST) under pH and temperature mimicking human body conditions.