Registration Dossier

Diss Factsheets

Administrative data

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

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 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

Test material

Constituent 1
Chemical structure
Reference substance name:
Zirconium carbide
EC Number:
235-125-1
EC Name:
Zirconium carbide
Cas Number:
12070-14-3
Molecular formula:
CZr
IUPAC Name:
zirconium carbide
Details on test material:
Batch No.: 25051/13
Purity: > 97 %
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: not applicable
Vehicle:
other: not applicable
Details on exposure:
not applicable
Duration and frequency of treatment / exposure:
not applicable
Doses / concentrations
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

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 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.

Any other information on results incl. tables

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

---

Applicant's summary and conclusion

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

---

Categories Display