Titanium nitride

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2014-09-19 to 2015-02-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

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 titanium nitride in body fluid simulants as a surrogate for bioavailability.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Titanium nitride

EC Number:

247-117-5

EC Name:

Titanium nitride

Cas Number:

25583-20-4

Molecular formula:

NTi

IUPAC Name:

titanium nitride

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): Titanium nitride
- Substance type: inorganic
- Analytical purity: 76.8 % titanium

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

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:

Titanium nitride was extracted in simulated leaching fluids for two time points: 2 hrs and 24 hrs. 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 titanium using EPA Method #200.8 (ICP/MS). Results were reported as µg Ti/g sample and as % Ti release/Ti 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 below (Table 1-5)

Any other information on results incl. tables

Table 1: Soluble Titanium in Simulated Gastric Fluid

Extraction	Weight used (g)	µg Titanium/ g Sample	% Titanium release/ Titanium content
2 hours	0.1014	2,643	0.34
(dup)	0.1012	2,619	0.34
24 hours	0.1021	17,777	2.31
(dup)	0.1024	18,138	2.36

 

Table 2: Soluble Titanium in Simulated Interstitial Fluid

Extraction	Weight used (g)	µg Titanium/ g Sample	% Titanium release/ Titanium content
2 hours	0.1003	<50	-
(dup)	0.1017	<50	-
24 hours	0.1011	<50	-
(dup)	0.1023	<50	-

 

Table 3: Soluble Titanium in Simulated Lysosomal Fluid

Extraction	Weight used (g)	µg Titanium/ g Sample	% Titanium release/ Titanium content
2 hours	0.1028	269	0.04
(dup)	0.1006	270	0.04
24 hours	0.1015	842	0.11
(dup)	0.1010	827	0.11

 

Table 4: Soluble Titanium in Artificial Perspiration

Extraction	Weight used (g)	µg Titanium/ g Sample	% Titanium release/ Titanium content
2 hours	0.1003	<50	-
(dup)	0.1019	<50	-
24 hours	0.1006	82	0.01
(dup)	0.1010	97	0.01

Table 5: Soluble Titanium in PBS

Extraction	Weight used (g)	µg Titanium/ g Sample	% Titanium release/ Titanium content
2 hours	0.1033	<50	-
(dup)	0.1007	<50	-
24 hours	0.1003	53	0.01
(dup)	0.1006	61	0.01

Applicant's summary and conclusion

Conclusions:

The release of titanium ions from titanium nitride is low in artifical body fluids. The more acidic the simulated fluid, the more titanium ions are released, i.e. 2.34 % titanium in simulated gastric fluid (pH 1.5) and 0.11 % in simulated lysosomal fluid (pH 4.5) after 24 hours.

Executive summary:

This report measured bioaccessibility of titanium nitride as a surrogate for bioavailability. Soluble titanium was measured using the EPA method #200.8 (ICP/MS) after incubation of titanium nitride in simulated body fluids (simulated gastric fluid, simulated interstitial fluid, simulated lysosomal fluid, and artificial perspiration). Results were reported as µg Ti/g sample and % Ti release/Ti content.

Overall, 24 hours of extraction time resulted in higher values of solved titanium as after 2 hours of extraction time. The amount of solved titanium, given as µg Ti/g sample and % Ti release/Ti content are summarized in the table below (mean values of the duplicates):

Simulated Body Fluid	pH	Extraction Time	µg Ti/ g sample	% Ti release/ Ti content
Gastric fluid	pH 1.5	2 h	2,631	0.34
		24 h	17,96	2.34
Intersitital fluid	pH 7.4± 0.2	2 h	<50	BDL
		24 h	<50	BDL
Lysosomal fluid	pH 4.5-5.0	2 h	270	0.04
		24 h	835	0.11
Artificial Perspiration	pH 6.5 ± 0.1	2 h	<50	BDL
		24 h	89.5	0.01

BDL: Below detection limit. In summary, release of titanium ions from titanium nitride is highest at acidic pH 1.5. The bioavailability in the fluids ranged from BDL (simulated interstitial fluid and artifical perspiration) to 2.34 % (simulated gastric fluid, 24 h extraction). Based on the results, the bioavailability of titanium nitride would be expected to be low and depends on the route of administration.