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Toxicological information

Basic toxicokinetics

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basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
Not reported
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Not sufficient detail to be able to assess the reliability.

Data source

Reference Type:
Tantalum Oxide, Silica and Latex: Effects on Alveolar Macrophage Viability and Lysozyme Release.
Matthey R A, Balzer P A, Putman C E, Gee B L, Beck G J & Greenspan R H
Bibliographic source:
Investigative Radiology 13(6) 514-518

Materials and methods

Objective of study:
Test guideline
no guideline followed
Principles of method if other than guideline:
Not a standard in vitro OECD method. Alveolar macrophages were incubated in medium with the test material for a total of 30 hours. Observations were made on cells viability, phagocytosis and lysozyme release.
GLP compliance:

Test material

Test material form:
solid: particulate/powder
migrated information: powder
Details on test material:
- Tantalum oxide,
- Mean particle diameter: 1 micron

Test animals

New Zealand White
not specified
Details on test animals and environmental conditions:
- Alveolar Marcophage cells.

- Weight of animals before harvesting the cells: 3-4lbs
- Cell acquisition: Alveolar macrophages were obtained from the rabbits by pulmonary lavage

Administration / exposure

Route of administration:
other: in vitro
Duration and frequency of treatment / exposure:
Incubation for a total of 30 hours.
Doses / concentrations
Doses / Concentrations:
300 µg/ml
Control animals:
yes, concurrent no treatment
Positive control:
Silica was used as a positive control, as it is known to be cytotoxic to alveolar macrophages.
Details on study design:
- Ten million cells were incubated for a total of 30 hours with the test material in medium.

- Latex was used as a negative control as it is considered to be inert and nontoxic to alveolar marchrophages.

- By pulmonary Lavage with Hanks Balanced Salt Solution (Gibco), this contained 100µg penicillin and 100µg streptomycin.
- The Lavage fluid was allowed to cool then centrifuged at 2000 rpm for 15 mins.
- The cell pellet was suspended in serum free medium 199 (Gibco), this contained penicillin and streptomycin. The cell count was performed using a Neubauer Bright Line heamocyteometer.
- Ten million cells were incubated in tissue culture flasks at 37ºC in an atmosphere of 95% CO2 for 48 hours.
- The medium was changed and the cells were then exposed to the test material.

- The cells were analysed at the following time points; 2, 6, 12, 24 and 30 hours.
- The cells were checked for viability, phagocytosis and lysozyme release.
- Cell viability, was checked using three different methods
1) The trypan blue exclusion test.
2) By release into the medium of the soluble cytoplasmic enzyme, LDH (lactate dehydrogenase).
3) By calculating the percentage of cells remaining adherent.
- Phagocytosis was evaluated by calculating the phaocytic index: expressing as a percentage of the cells containing particles, 500 cells were counted per flask.
- Lysozyme release into medium was determined as an index of hydrolytic enzyme discharge from the cell culture in response to phagocytic challenge.

NUMBER OF REPLICATIONS: Three experiments were performed and the mean value taken.
- One way analysis of variance was used to compare the treatment responses at each time point.
- Two tail test on treatment pairs with an adjusted significance level to control the overall level at 0.05.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
At two hours, > 90% of the alveolar macrophage cells had ingested the test material.

Any other information on results incl. tables


The test material is toxic to alveolar macrophage cells in vitro, determined by the significantly increased release if LDH at 12, 24 and 30 hours. The toxic effect of the test material were less rapid than that of silica (positive control). This toxicity is thought to partly cause the delayed clearance of the lungs.

The author concluded, based on this data, that the test material would also be toxic in vivo.

Applicant's summary and conclusion

Interpretation of results (migrated information): low bioaccumulation potential based on study results.
This study indicates that there is a low potential for bioaccumulation of the test material when exposed via inhalation. > 90% of Tantalum oxide was ingested via alveolar macrophage cells within two hours of exposure. Delayed clearance of the dust particles occurs due to the toxic effects of Tantalum oxide. The study concluded that the test material would have similar effects in vivo.
Executive summary:

The clearance of the test material by alveolar macrophage cells was determined in a non GLP-compliant study which was performed to a none standard OECD method. The cells were exposed to the test material in vitro and observed for 30 hours after introduction of the test material. It was shown that > 90% of the test material was ingested by the alveolar macrophage cells within the first two hours. Delayed clearance by the cells was a result of the toxic effects of the test material. The study concluded that the test material would have similar effects in vivo.