Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
January to March 2012
Reliability:
2 (reliable with restrictions)
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:
2012
Report Date:
2012

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Titanium Carbide
- Substance type: inorganic
- Physical state: solid
Radiolabelling:
no

Test animals

Species:
other: not applicable
Strain:
other: not applicable
Details on test animals 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
Remarks:
Doses / Concentrations:
0.1 g of test substance in 50 mL of simulated fluid
No. of animals per sex per dose:
Not applicable
Control animals:
other: not applicable
Positive control:
Not applicable
Details on study design:
Titanium Carbide was extracted in leaching fluids for different time periods: 2hrs and 24 hrs in simulated gastric and lysosomal fluid, 24 hrs in simulated interstitial fluid and 12 hrs in artifical 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°C was used. All extractions were performed in triplicate. The extracts were analyzed for soluble Titanium using EPA Method #200.7 (ICP). Results were reported as ug Ti/g sample, % Ti/g sample and as % of total available Ti released.
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

Any other information on results incl. tables

Table 1: Soluble Titanium in gastric fluid

Extraction time in h

Weight used

µg Titanium/g Sample

% Titanium release/Titanium content

2

0.1008

1,637

0.20

(dup)

0.1058

1,749

0.22

(trip)

0.1034

1,644

0.21

24

0.1021

4,603

0.58

(dup)

0.1024

4,395

0.55

(trip)

0.1042

4,319

0.54

 

Table 2: Soluble Titanium in simulated interstitial fluid

Extraction time in h

Weight used

µg Titanium/g Sample

% Titanium release/Titanium content

24

0.1027

< 50.0

-

(dup)

0.1004

< 50.0

-

(trip)

0.1024

< 50.0

-

 

Table 3: Soluble Titanium in lysosomal fluid

Extraction time in h

Weight used

µg Titanium/g Sample

% Titanium release/Titanium content

2

0.0992

151

0.02

(dup)

0.0995

151

0.02

(trip)

0.1015

148

0.02

24

0.1029

656

0.08

(dup)

0.0995

678

0.08

(trip)

0.1005

662

0.08

 

Table 4: Soluble Titanium in artificial perspiration

Extraction time in h

Weight used

µg Titanium/g Sample

% Titanium release/Titanium content

12

0.0996

< 50.0

-

(dup)

0.1052

< 50.0

-

(trip)

0.1006

< 50.0

-

 

Applicant's summary and conclusion

Conclusions:
The release of Ti ions from TiC is very low in artifical body fluids. More Ti ions are released at acidic pH with up to 0.56 % in simulated gastric acid solution (pH 1.5) and 0.08 % in lysosomal fluid (pH 4.5).
Executive summary:

This report measured bioaccessibility of Titanium Carbide as a surrogate for bioavailability.To do this the soluble Titanium was measured using the EPA method #200.7 (ICP) after incubation of Titanium Carbide in simulated body fluids (simulated gastric fluid, simulated interstitial fluid, simulated lysosomal fluid, and artifical perspiration). Results were reported as ug Ti/g sample, % Ti/g sample and as % of total available Ti released.

Overview of Ti released in the different simulated body fluids:

Medium

t in h

% Ti-release

Simulated gastric fluid

2

0,21 %

24

0,56 %

Simulated interstitial fluid

24

BDL

Simulated lysosomal fluid

2

0,02%

24

0,08 %

Artifical perspiration

12

BDL

BDL: Below detection limit. In summary, release of Titanium ions from TiC is higher at acidic pH, even though at a very low degree. The bioavailability in the fluids ranged from BDL (interstitial fluid and artifical perspiration) to 0,56 % (simulated gastric fluid). Thus, the maximum solubility was determined at acidic pH. Based on the results, the bioavailability of Titanium carbide would be expected to be low for all routes of administration.