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Toxicological information

Basic toxicokinetics

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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 pentoxide.

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

Constituent 1
Chemical structure
Reference substance name:
Diniobium pentaoxide
EC Number:
215-213-6
EC Name:
Diniobium pentaoxide
Cas Number:
1313-96-8
Molecular formula:
Nb2O5
IUPAC Name:
diniobium(5+) pentaoxidandiide
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 pentoxide 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. 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 test item 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 hours. 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).
o the residual, undissolved test item in the vessels, 80 mLaqua regia (3:1 mixture of concentrated hydrochloric andnitric acid) were added
to the flasks after the test. The filter used for sampling were extensively rinsed with aqua regia. Solutions weresampled 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:
The objective of the present test was to investigate the dissolution of niobium pentoxide 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. 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 test item 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 hours. 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).

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.


Doses / concentrations
Remarks:
Doses / Concentrations:
Each test flask was loaded with 100 mg/L of test item.
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 (n=3)
ASW 2h (duplicate samples, a and b) / 1.889 ± 0.174
ASW 24h (duplicate samples, a and b) / 6.992 ± 0.457
GST 2h (duplicate samples, a and b) / 0.356 ± 0.047
GST 24h (duplicate samples, a and b) / 1.059 ± 0.088

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 <1% 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.
vessel 1 ± SD

Nb conc. [µg/L]
vessel 2

mean Nb conc.
vessel 2 ± SD

Nb conc. [µg/L]
vessel 3

mean Nb
conc.
vessel 3 ± SD

mean Nb conc. all vessels ± SD

ASW2h a

1.683

1.690 ± 0.010

2.044

2.074 ± 0.043

1.894

1.904 ± 0.014

1.889 ± 0.174

ASW2h b

1.697

2.104

1.914

ASW24h a

6.685

6.822 ± 0.193

7.157

7.150 ± 0.010

6.335

7.005 ± 0.948

6.992 ± 0.457

ASW24h b

6.958

7.144

7.675

 

 

 

 

 

 

 

 

GST 2h a

0.305

0.307 ± 0.003

0.409

0.412 ± 0.005

0.357

0.349 ± 0.011

0.356 ± 0.047

GST 2h b

0.309

0.415

0.342

GST 24h a

1.159

1.114 ± 0.064

1.108

1.112 ± 0.006

0.936

0.952 ± 0.023

1.059 ± 0.088

GST 24h b

1.069

1.116

0.969

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 of aqua regia
[µg/L]

loading
[mg]

loading in relation to Nb
(69.90 % Nb in test item)
[mg]

recovery
[%]

ASW vessel 1

7.81

100.69

70.38

< 1

ASW vessel 2

8.01

101.01

70.61

< 1

ASW vessel 3

12.0

101.14

70.70

< 1

 

 

 

 

 

GST vessel 1

4.68

100.52

70.26

< 1

GST vessel 2

3.73

101.81

71.17

< 1

GST vessel 3

3.92

100.32

70.12

< 1

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: Niobium was hardly 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 pentoxide 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 hardly soluble in artificial sweat solution (ASW) nor in artificial gastric fluid (GST) under pH and temperature mimicking human body conditions.