Niobium dioxide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-08-17 to 2017-01-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods

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:

no guideline available

Principles of method if other than guideline:

This report measured bioaccessibility of Niobium dioxide in body fluid simulants as a surrogate for bioavailability.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Niobium dioxide

EC Number:

234-809-7

EC Name:

Niobium dioxide

Cas Number:

12034-59-2

Molecular formula:

NbO2

IUPAC Name:

niobium oxide

Test material form:

solid

Details on test material:

Batch No.: SB15003
Purity: > 99 %

Radiolabelling:

no

Test animals

Species:

other: not applicable

Strain:

other: not applicable

Sex:

not specified

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

Doses / concentrations 1

Dose / conc.:

0.2 other: g/L

Remarks:

Loading (Gastric bio-elution test)

Doses / concentrations 2

Dose / conc.:

2 other: g/L

Remarks:

Loading (Sweat bio-elution test)

Doses / concentrations 3

Dose / conc.:

2 other: g/L

Remarks:

Loading (Alveolar bio-elution test)

Doses / concentrations 4

Dose / conc.:

2 other: g/L

Remarks:

Loading (Lyosomal bio-elution test)

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:

Please see box "Any other information on materials and method incl. tables"

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

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

The results of the bio-elution tests (see tables 1-5 in box "Any other information on results incl. tables") of Niobium dioxide showed a consistent very low metal release in all the arteficial media tested. The highest metal release concentration was found in artificial lysosomal fluid with < 0.1% after 72 hours of incubation.

Any other information on results incl. tables

Table 1: Summary of Results

Metal release in Gastric test (µg/L)				% Solubility (0.2 g/L loading)
2 h		CV, %		2 h	CV, %
1.27		13		0.00086	13
Metal release in Lyosomal fluid (µg/L)				% Solubility (2 g/L loading)
24 h	CV, %	72 h	CV, %	72 h	CV, %
322.0	3	956.2	3	0.065	3
Metal release in Alveolar fluid (µg/L)				% Solubility (2 g/L loading)
24 h	CV,%	72 h	CV, %	72 h	CV, %
128.1	7	127.3	12	0.009	12
Metal release in Perspiration fluid (µg/L)				% Solubility (2 g/L loading)
24 h	CV, %	168 h	CV, %	168 h	CV, %
57.0	7	171.5	1	0.012	1

Table 2: Results of the Gastric bio-elution test

Gastric test parameters				Niobium, µg/L
	Time [h]	T [°C]	pH	Mean	SD	CV [%]
Blanks	0	37	1.50	0.10	0.026	26
	2	37	1.50	BDL	-	-
Nb(IV) oxide	0	37	1.50	BDL	-	-
	2	37	1.50	1.27	0.17	13

CV corresponds to the coefficient of variation between vessels. BDL: Below detection limit. Nb values reported in Blanks for all 3 vessels were below the practical quantitation level for the gastric media (PQL = 0.35 μg/L).

Table 3: Results of the Lyosomal bio-elution test

Lyosomal test parameters				Niobium, µg/L
	Time [h]	T [°C]	pH	Mean	SD	CV [%]
Blanks	0	37	4.50	BDL	-	-
	2	37	4.48	BDL	-	-
	24	37	4.47	BDL	-	-
	72	37	4.45	BDL	-	-
Nb(IV) oxide	0	37	4.50	BDL	-	-
	2	37	4.45	62.2	0.51	1
	24	37	4.42	322.0	8.2	3
	72	37	4.45	956.2	26.1	3

CV corresponds to the coefficient of variation between vessels. BDL: Below detection limit.

Table 4: Results of the Alveolar bio-elution test

Alveolar test parameters				Niobium, µg/L
	Time [h]	T [°C]	pH	Mean	SD	CV [%]
Blanks	0	37	7.41	BDL	-	-
	2	37	7.27	BDL	-	-
	24	37	7.29	BDL	-	-
	72	37	7.40	BDL	-	-
Nb(IV) oxide	0	37	7.41	BDL	-	-
	2	37	7.40	25.7	1.3	5
	24	37	7.41	128.1	9.0	7
	72	37	7.42	127.3	15.3	12

CV corresponds to the coefficient of variation between vessels. BDL: Below detection limit. Nb values reported in the Blanks were equal to or below the practical quantitation level for the Alveolar media (PQL = 1.0 μg/L).

Table 5: Results of the Sweat bio-elution test

Alveolar test parameters				Niobium, µg/L
	Time [h]	T [°C]	pH	Mean	SD	CV [%]
Blanks	0	30	6.45	BDL	-	-
	24	30	6.30	BDL	-	-
	168	30	5.97	BDL	-	-
Nb(IV) oxide	0	30	6.45	BDL	-	-
	24	30	6.31	57.0	4.0	7
	168	30	6.51	171.5	2.3	1

CV corresponds to the coefficient of variation between vessels. BDL: Below detection limit.

Applicant's summary and conclusion

Conclusions:

The release of niobium ions from Niobium dioxide is very low in artifical body fluids. Based on the results, the bioavailability of Niobium dioxide can be considered to be very low for all routes of administration.

Executive summary:

A study to estimate bioaccessibility of Niobium dioxide in different artificial media: gastric juice, lysosomal, alveolar and perspiration fluids; representing ingestion, inhalation and dermal contact routes of exposure in humans, was performed. The rate and extend of the metal released in these in vitro simulations of biological compartments can be used for human health hazard classification of this substance.

The results showed a consistent very low metal release in all the arteficial media tested. The highest niobium release concentration was found in lysosomal fluid with ca.0.1% after 72 hours of incubation. Metal release (μg/L) and solubility results (percentage) are summarized in the Table below.

Simulated Body Fluid	pH	Extraction Time (h)	µg Nb/L sample	% Nb release
Gastric fluid	1.5	2	1.27	0.00086
Lyosomal fluid	4.5 - 5.0	24	322.0	-
		72	956.2	0.065
Alveolar fluid	7.4	24	128.1	-
		72	127.3	0.009
Perspiration fluid	6.5	24	57.0	-
		268	171.5	0.012