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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Dissolution of Functional Materials and Rare Earth Oxides into Pseudo Alveolar Fluid
Author:
Takaya M, Shinohara Y, Serita F, Ono-Ogasawara M, Otaki N, Toya T, Takata A, Yoshida K, Kohyama N
Year:
2006
Bibliographic source:
Indstrial Health, 44, 639-644

Materials and methods

Objective of study:
other: bioavailability in physiological fluids
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
An in vitro dissolution bioavailability test was performed with Lanthanum trioxide in water, physiological saline and Gambles fluid simulating alveolar fluid affter an incubation of 1 and 7 days.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Lanthanum oxide
- Molecular formula : La2O3
- Analytical purity: 99.9%
- Source: Kojndo Chemical (Sakado, Japan)
Radiolabelling:
no

Administration / exposure

Details on study design:
Solvents: Pure water with a conductivity of 18.2 M-Ohm, physiological saline prepared from the same water, modified Gambles fluid:
MgCl2x6 H2O       0.212 g/l
NaCl                     6.415 g/l
CaCl2x2 H2O        0.255 g/l
Na2SO4               0.079 g/l
Na2HPO4             0.148 g/l
NaHCO3              2.703 g/l
Na-hydrogentartrate dihydrate 0.18 g/l
Na-dihydrogen citrate dihydrate 0.153 g/l
Na-lactate       0.175 g/l
Na-pyruvate            0.172 g/l
Glycine              0.118 g/l
The solution was adjusted to pH 7.6 with hydrochloric acid.

Lanthanum oxide was purchased from Kojundo Chemical Laboratory (Sakado, Japan). Purity > 99.9 %. The particle size was determined using scanning electron microscopy (SEM; S-4700). The D50 was 1.89 micro-m and the geometric standard derivation 1.85.
Preparation of solutions and analysis:
To 0.5 g of the Lanthanumoxide 40 ml of the respective fluid was added in a 50 ml polyethylene centrifuge tube and the tubes kept at a constant temperature of 23 deg. C. After 1 and 7 days of incubation 1 ml samples were taken from the solution, filtered through a 0.45 micro-m millipore filter and the filtrate stabilised by addtion of 9 ml of a 6% nitric acid solution. The Lanthanum concentration was measured by inductive coupled mass spectrometry (Agilent).

Results and discussion

Any other information on results incl. tables

Lanthanum ion concentrations were not detectable (detection limit not indicated) in water and saline. Concentrations in Gambles solution were 3.4 ppb and 17.3 ppb after 1 and 7 days respectively.

A comparble experiment was also performed with Ceriumdioxide of a low particle size (D50: 0.2 micro-m, geometric standard deviation 1.0). Cerium metal ions were also below the detection limit in water and saline and the concentration in Gamble's solution were 3.3 and 217.9 micro-g after 1 and 7 days respectively.           

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
Lanthanum oxide was essentially insoluble in water and physiological saline and had a very low solubility in modified Gamble's solution simulating alveolar fluid. From this experiment it can be concluded that the systemic availability of Lanthanum from Lanthanum oxide after inhalation exposure will be low.
Executive summary:

Takaya et al (2006) performed an in vitro dissolution bioavailability test with Lanthanum trioxide (purity >99.9%, particle size (by electron microscopy) D50 1.89 micro-m) in water, physiological saline and modified Gambles fluid simulating alveolar fluid affter an incubation of 1 and 7 days. Lanthanum was below the detection limit in water and saline and in Gamble's fluid the concentration was 3.5 micro-g/L after 1 day and 17.3 micro-g/L after 7 days. The maximum solubility was 0.00016% after 7 days in alveolar simulation fluid.From this experiment it can be concluded that the systemic availability of Lanthanum from Lanthanum oxide after inhalation exposure will be low.