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Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2016
Reliability:
1 (reliable without restriction)
Reference:
Composition 0
Objective of study:
distribution
toxicokinetics
Qualifier:
no guideline followed
Principles of method if other than guideline:
Refer to the full paper in material and methods section.
The objective of the study was to compare the effects of intravenous and oral administration of metal on the organism (male albino Wistar rats).
GLP compliance:
no
Specific details on test material used for the study:
Titanium(IV) citrate (C18H12NaO21Ti-7)
Species:
rat
Strain:
Wistar
Sex:
male
Conclusions:
The study made by the team of Golasik (2016) shows that titanium in ionic form has low oral bioavailability (3.8%) and is poorly absorbed into the circulation.

The Ti concentration 3 h after intravenous administration was about 100 times higher in serum, 10 times higher in kidneys and spleen, 8 times higher in liver than after the same time following 30-days repeated intragastric administration. The main organ for titanium deposition after administration of a soluble salt is kidney. This result might be related to the role of the kidneys with the elimination of this form of metal. The present results suggest that the exposure to ionic titanium should not result in excessive accumulation of metal in the organism.
Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2013
Reliability:
2 (reliable with restrictions)
Reference:
Composition 0
Objective of study:
toxicokinetics
Qualifier:
no guideline followed
Principles of method if other than guideline:
For further details on the material and methods - refer to the full paper
GLP compliance:
no
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
For further details on the material and methods - refer to the full paper
Route of administration:
oral: gavage
Vehicle:
water
Details on absorption:
The concentration of Ti in the blood samples of rats treated with TiO2 for 13 weeks was 0.4–0.5 μg/g and the differences between the values of the control and highdose groups were less than 0.1 μg/g. Considering that the dose for the high-dose group was 1041.5 mg/kg body weight, TiO2 nanoparticles might have an extremely low absorption rate.
Details on distribution in tissues:
TiO2 distribution to the liver, spleen, kidney, and brain was also minimal. No dose-response relationship was seen, meaning that the TiO2 particles were not significantly distributed. This low distribution was due to the minimal absorption rate.
Metabolites identified:
not measured
Conclusions:
The team of Cho et al. (2013) studied the absorption, distribution and excretion pattern of the nanoform of titanium dioxide (TiO2). Nanoparticles were orally administered to Spradue-Dawley rats for 13 weeks (7 days/week). Samples of blood, tissues (liver, kidneys, spleen, and brain), urine, and feces were obtained at necropsy. The level of Ti in each sample was measured using inductively coupled plasma-mass spectrometry. From this experiment, it appears that TiO2 nanoparticles had extremely low absorption. Tissue distribution data showed that TiO2 nanoparticles were not significantly increased in sampled organs, even in the group receiving the highest dose (1041.5 mg/kg body weight). In addition, Ti concentrations were not significantly increased in the urine while very
high concentrations of Ti were detected in the feces. These results were explained by the low solubility of TiO2 nanoparticles. Based on this study, TiO2 has a low absorption potential in the body of rats after oral exposure.

Description of key information

* Toxicokinetic of the soluble form of Ti (Ti4 +)

The study made by the team of Golasik (2016) shows that titanium in ionic form, has low oral bioavailability (3.8%) and is poorly absorbed into the circulation. The animals were administered either a single intravenous dose of 6 mg Ti/kg b.w., or received the same dose orally every day for 30 days. The concentration of titanium in the serum and organs was measured by a graphite furnace atomic absorption spectrometry. Metal rapidly distributed from the circulation to the investigated organs after both routes of administration, and kidney was identified as the main target tissue, followed by liver and spleen. One month of oral exposure to Ti led to the increase of its concentration in liver, kidneys, spleen, and heart. In the intravenous study, both the highest area under concentration-time curves and the longest elimination half-life time were recorded in the kidney followed by serum, spleen and liver.

Having the kidneys as the main organ impacted, it has been hypothetised that the organ was actually inolved in the elimination of this form of metal. In conclusion, the present results suggest that the exposure to ionic titanium should not result in excessive accumulation of metal in the organism.

* Toxicokinetic of the insoluble form of TiO2 (Nanoform)

The team of Cho et al. (2013) studied the absorption, distribution and excretion pattern of of the nanoform of titanium dioxide (TiO2). Nanoparticles were orally administered to Spradue-Dawley rats for 13 weeks (7 days/week). Samples of blood, tissues (liver, kidneys, spleen, and brain), urine, and feces were obtained at necropsy. The level of Ti in each sample was measured using inductively coupled plasma-mass spectrometry. From this experiment, it appears that TiO2 nanoparticles had extremely low absorption. Tissue distribution data showed that TiO2 nanoparticles were not significantly increased in sampled organs, even in the group receiving the highest dose (1041.5 mg/kg body weight). In additon, Ti concentrations were not significantly increased in the urine while very high concentrations of Ti were detected in the feces. These results were explained by the low solubility of TiO2 nanoparticles. Based on this study, TiO2 has a low absorption potential in the body of rats after oral exposure.

* Overall conclusion:

From both forms of Ti (Soluble and insoluble) - Low absorption have been recorded in rats exposed orally following repeated doses. These data have been used to extrapolate the toxicokinetic of the insoluble titanium hydride.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information