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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:
2013-12-05 to 2014-02-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment.

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:
no guideline available
Deviations:
not applicable
Principles of method if other than guideline:
This report measured bioaccessibility of tantalum carbide in body fluid simulants as a surrogate for bioavailability.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Tantalum carbide
EC Number:
235-118-3
EC Name:
Tantalum carbide
Cas Number:
12070-06-3
Molecular formula:
CTa
IUPAC Name:
tantalum carbide
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Tantalum Carbide
- Analytical purity: 93.8% Tantalum

Radiolabelling:
no

Test animals

Species:
other: not applicable
Strain:
other: not applicable
Details on test animals or test system and environmental conditions:
not applicable

Administration / exposure

Route of administration:
other: in vitro study
Vehicle:
other: in vitro study
Details on exposure:
not applicable
Duration and frequency of treatment / exposure:
not applicable
Doses / concentrations
Remarks:
Doses / Concentrations:
0.1 g of test substance in 50 mL of simulated fluid
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:
Tantalum carbide was extracted in leaching fluids for different time periods: 2 hrs and 24 hrs in simulated gastric and lysosomal fluid, 24 hrs in simulated interstitial fluid and 12 hrs in artificial perspiration. The extractions were performed using 0.1 gram of sample in 50 ml of simulated fluid. A shaker water bath at a temperature of 37± 2°C was used. All extractions were performed in duplicate. The extracts were analyzed for soluble Tantalum using EPA Method #200.8 (ICP/MS). Results were reported as µg Ta/g sample, % Ta/g sample and as % of total Ta released/Tantalum content.
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:
see tables in section " any other information on results incl. tables"

Any other information on results incl. tables

Table 1: Soluble Tantalum in Gastric fluid

Extraction time in h

Weight used

µg Tantalum /g Sample

% Tantalum release/ Tantalum content

2 hours

0.1034

<25.0

--

(dup)

0.1010

<25.0

--

24 hours

0.1059

<25.0

--

(dup)

0.1007

<25.0

--

 

Table 2: Soluble Tantalum in Interstitial fluid

Extraction time in h

Weight used

µg Tantalum /g Sample

% Tantalum release/ Tantalum content

2 hours

0.1000

<25.0

--

(dup)

0.1008

<25.0

--

24 hours

0.1043

<25.0

--

(dup)

0.1016

<25.0

--

 

Table 3: Soluble Tantalum in Lysosomal fluid

Extraction time in h

Weight used

µg Tantalum /g Sample

% Tantalum release/ Tantalum content

2 hours

0.1036

<25.0

--

(dup)

0.1024

<25.0

--

24 hours

0.1042

43.0

0.005

(dup)

0.1048

33.0

0.004

 

Table 4: Soluble Tantalum in Artificial Perspiration

Extraction time in h

Weight used

µg Tantalum /g Sample

% Tantalum release/ Tantalum content

2 hours

0.1010

<25.0

--

(dup)

0.1019

<25.0

--

24 hours

0.1032

<25.0

--

(dup)

0.1014

<25.0

--

 

Table 5: Soluble Tantalum in PBS

Extraction time in h

Weight used

µg Tantalum /g Sample

% Tantalum release/ Tantalum content

2 hours

0.1037

<25.0

--

(dup)

0.1051

<25.0

--

24 hours

0.1008

25.0

0.003

(dup)

0.1040

34.0

0.004

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
The release of tantalum ions from tantalum carbide is very low in artificial body fluids. For simulated gastric fluid, simulated interstitial fluid and arteficial perspiration no release of tantalum ions was observed as the results were below the detection limit of the method.
Only in simulated lysosomal fluid 0.005% tantalum ions were released within 24 hours from tantalum carbide.
Executive summary:

This report measured bioaccessibility of tantalum carbide as a surrogate for bioavailability. Thus, the soluble tantalum was measured by using EPA Method #200.8 (ICP/MS) after incubation of tantalum carbide in different simulated body fluids (simulated gastric fluid, simulated interstitial fluid, simulated lysosomal fluid, and artificial perspiration). Results were reported as µg Ta/g sample, % Ta release/Ta content.

 

Overview of Tantalum released in the different simulated body fluids:

Medium

t in h

% Ta-release

Simulated gastric fluid

2

BDL

24

BDL

Simulated interstitial fluid

2

BDL

24

BDL

Simulated lysosomal fluid

2

BDL

24

0,005%

Artificial perspiration

2

BDL

24

BDL

PBS

2

BDL

24

0,004%

BDL – Below method detection limit

 

In summary, release of tantalum ions from tantalum carbide is very low. The actually measured release of tantalum in lysosomal fluid is in the same magnitude as the reference fluid (PBS). Based on the results, the bioavailability of tantalum carbide is expected to be very low for all routes of administration.