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Reference
Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2013-10-08 to 2014-02-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Objective of study:
bioaccessibility (or bioavailability)
Qualifier:
no guideline followed
Principles of method if other than guideline:
This report measured bioaccessibility of Zirconium carbide in body fluid simulants as a surrogate for bioavailability.
GLP compliance:
no
Radiolabelling:
no
Species:
other: not applicable
Strain:
other: not applicable
Sex:
not specified
Details on test animals or test system and environmental conditions:
not applicable
Route of administration:
other: not applicable
Vehicle:
other: not applicable
Details on exposure:
not applicable
Duration and frequency of treatment / exposure:
not applicable
Remarks:
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:
Please see box "Any other information on materials and method incl. tables"
Details on dosing and sampling:
not applicable
Statistics:
not applicable
Preliminary studies:
not applicable
Details on absorption:
not applicable
Details on distribution in tissues:
not applicable
Details on excretion:
not applicable
Metabolites identified:
not measured
Details on metabolites:
not applicable
Bioaccessibility (or Bioavailability) testing results:
The results of the bio-elution tests (see Table 1 in box "Any other information on results incl. tables") of Zirconium carbide in general showed a very low solubility in the set of fluids assayed.

Table 1: Results of bio-elution tests

Extraction Time

Weight Used (g)

µg Zirconium /

g Sample

% Zirconium Release/ Zirconium Content

Simulated Gastric Fluid

2 hours

0.1004

<25.0

---

                 (dup)

0.1008

<25.0

---

24 hours

0.1001

<25.0

---

                 (dup)

0.1006

<25.0

---

Simulated Interstitial Fluid

2 hours

0.1016

<25.0

---

                 (dup)

0.1016

<25.0

---

24 hours

0.1005

<25.0

---

                 (dup)

0.1016

<25.0

---

Simulated Lysosomal Fluid

2 hours

0.1002

35.0

0.004

                 (dup)

0.1008

<25.0

---

24 hours

0.1012

40.0

0.005

                 (dup)

0.1028

39.0

0.005

Artificial Perspiration

2 hours

0.1001

<25.0

---

                 (dup)

0.1008

<25.0

---

24 hours

0.1009

<25.0

---

                 (dup)

0.1005

<25.0

---

PBS

2 hours

0.1006

<25.0

---

                 (dup)

0.1009

<25.0

---

24 hours

0.1003

<25.0

---

                 (dup)

0.1004

<25.0

---

Conclusions:
The release of zirconium ions from Zirconium carbide was very low in artificial body fluids. For simulated gastric fluid, simulated interstitial fluid and arteficial perspiration no release of zirconium ions was observed as the results were below the detection limit of the method. Only in simulated lysosomal fluid 0.005% zirconium ions were released within 24 hours from Zirconium carbide.
Executive summary:

This report measured bioaccessibility of Zirconium carbide as a surrogate for bioavailability. Thus, the soluble zirconium was measured by using EPA Method #200.8 (ICP/MS) after incubation of Zirconium carbide in different simulated body fluids (simulated gastric fluid, simulated interstitial fluid, simulated lysosomal fluid, and artificial perspiration). Results were reported as µg Zr/g sample, % Zr release/Zr content. The release of zirconium ions from Zirconium carbide was very low in artificial body fluids. The results of the study are summarized in the table below:

Extraction Time

Weight Used (g)

µg Zirconium /

g Sample

% Zirconium Release/ Zirconium Content

Simulated Gastric Fluid

2 Hours

0.1004

<25.0

---

                 (dup)

0.1008

<25.0

---

24 Hours

0.1001

<25.0

---

                 (dup)

0.1006

<25.0

---

Simulated Interstitial Fluid

2 Hours

0.1016

<25.0

---

                 (dup)

0.1016

<25.0

---

24 Hours

0.1005

<25.0

---

                 (dup)

0.1016

<25.0

---

Simulated Lysosomal Fluid

2 Hours

0.1002

35.0

0.004

                 (dup)

0.1008

<25.0

---

24 Hours

0.1012

40.0

0.005

                 (dup)

0.1028

39.0

0.005

Artificial Perspiration

2 Hours

0.1001

<25.0

---

                 (dup)

0.1008

<25.0

---

24 Hours

0.1009

<25.0

---

                 (dup)

0.1005

<25.0

---

PBS

2 Hours

0.1006

<25.0

---

                 (dup)

0.1009

<25.0

---

24 Hours

0.1003

<25.0

---

                 (dup)

0.1004

<25.0

---

Description of key information

The release of zirconium ions from Zirconium carbide was very low in artificial body fluids. For simulated gastric fluid, simulated interstitial fluid and artificial perspiration no release of zirconium ions was observed as the results were below the detection limit of the method. Only in simulated lysosomal fluid 0.005% zirconium ions were released within 24 hours from Zirconium carbide.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

Additional information

The bioaccessibility of Zirconium carbide as a surrogate for bioavailability was measured. For this purpose soluble zirconium ions were measured using the EPA method #200.8 (ICP/MS) after incubation of Zirconium carbide in different simulated body fluids (simulated gastric fluid, simulated interstitial fluid, simulated lysosomal fluid and artificial perspiration).

In summary, in all body fluids the release of zirconium ions was below the detection limit of the methodology used, except for the simulated lysosomal body fluid, in which the release of zirconium was measured with 0.005%. Based on the results, the bioavailability of Zirconium carbide can be considered to be very low for all routes of administration.

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