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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
Not reported
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies

Data source

Reference
Reference Type:
publication
Title:
Powdered Tantalum as a Medium for Bronchography in Canine and Human Lungs
Author:
Nadel JA, Wolfe WG & Graf PD
Year:
1968
Bibliographic source:
Invest. Radiol. Vol. 3: 229-238

Materials and methods

Objective of study:
distribution
excretion
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The immediate and long term effects on the lungs of dogs after insufflating with powdered tantalum were investigated. The lungs of dogs were artificially ventilated. Transpulmonary pressure, airflow, volume, pulmonary resistance and dynamic pulmonary compliance were measured. Blood samples were taken and carbon dioxide and oxygen tensions measured. Bronchograms were obtained by stopping ventilation temporarily and insufflating tantalum powder into the lungs. Deposition of tantalum in the lungs was monitored with a fluoroscope. The weight of tantalum at the start and the amount recovered from the apparatus after the bronchogram was measured and it was assumed that the weight lost was deposited in the lungs. Chest roentgenograms were obtained following bronchography and during various studies at the same time the mechanical properties of the lungs were measured. The roentgenograms followed the time course of excretion of powdered tantalum from the lungs after the bronchogram. Dogs were necropsied and the lungs studied microscopically.
GLP compliance:
not specified

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): pure tantalum powder

Test animals

Species:
dog
Strain:
not specified

Administration / exposure

Route of administration:
inhalation: dust
Vehicle:
unchanged (no vehicle)
Details on exposure:
TYPE OF INHALATION EXPOSURE: other:
-Immediate effects
The lungs were ventilated artificially with a Harvard respiratory pump connected to a tracheostomy tube.
-Long term effects
In this group, two methods were used: firstly, the animals were intubated temporarily with a cuffed endotracheal tube (No. 38-12F); secondly a polyethylene catheter (No. PE 260) was inserted into a bronchus.

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:
-Immediate effects
Air flow from a compressed air tank (range 0.65 to 1.35 L/s) was allowed to flow into a closed 1 L container that contained 80 g of powdered tantalum. The jet of air stirred the powder into a fine cloud; the tantalum powder flowed into the lungs via the tracheostomy tube and was deposited in the airways.
-Long term effects
In the first group, the tantalum powder was deposited into the lungs as part of a sterile bronchography procedure.
In the second group, a compressive rubber bulb was attached to a catheter which enters a 50 mL closed glass bottle containing powdered tantalum. When the insufflator bulb is squeezed, the airflow stirs the powder into a cloud and particles leave the bottle via a second catheter (in the airway of the animal) and deposit it in the airways. The powder deposits within 1 cm of the catheter tip; by moving it around, powder can be deposited selectively in various airways.

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: mean particle diameter by weight, 2.5 µm (range 0.33 - 3.7 µm)
Duration and frequency of treatment / exposure:
Each animal was subjected to a single bronchography procedure.
Doses / concentrations
Remarks:
Doses / Concentrations:
8 - 16 g of tantalum (0.5 - 1.0 mL) was required to outline the airways; this amount of material was deposited during 3 - 5 lung inflations in less than 2 minutes.
No. of animals per sex per dose:
31 animals in total were subjected to bronchography:
-20 animals were in the immediate effects category
-11 animals were in the long term effects group; of these, 4 took part in the endotracheal procedure and 7 via catheterisation.
Control animals:
no

Results and discussion

Preliminary studies:
The article reports on the inertness of tantalum stating that the lack of solubility and chemical inertness suggest that there should be little foreign-body or systemic reaction to tantalum.

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:
Airways of both lungs from trachea to bronchioles less than 1 mm in diameter were outlined without any evidence of tantalum in the alveoli. Bronchograms showed that total lung resistance increased as did dynamic pulmonary compliance and arterial pH whereas arterial CO2 and O2 decreased. None of these changes were viewed as significant.
Microscopic sections of airways taken immediately after bronchography showed a fine coating of tantalum outlining the airways with no evidence of inflammation. All animals recovered from bronchography without evidence of respiratory infection and survived until killed for pathologic examination.
Roentgenograms of the lungs showed that tantalum was cleared from airways larger than 1 mm in 2 -3 days, during which time tantalum was found in the stomach and intestines indicating that it had been carried up the airways and swallowed. In the walls of some airways less than 1 mm in diameter, there were small clusters of macrophages containing tantalum particles. These areas did not contain fibroblasts. In dogs killed at 23 and 38 days, small amounts of tantalum in peribronchiolar tissue of airways less than 1 mm in diameter were seen. There was no sign of tissue reaction in any area and lymph nodes did not contain tantalum.
Details on excretion:
Sequential roentgenograms showed complete clearing of the tantalum from the lungs within 4 days. Roentgenologic examination of the lungs post mortem confirmed the absence of tantalum in airways and lung parenchyma, and microscopic examination of the lungs 8 - 21 days after bronchography revealed no evidence of inflammation in airways or lung parenchyma.

Applicant's summary and conclusion

Conclusions:
In an experimamental inhalation study using dogs, tantalum was not found to cause unfavourable tissue reaction. When inhaled, there was no evidence of either acute or chronic inflammatory response in the airways or pulmonary tissue. Powdered tantalum delivered to the large airways was carried up the airways and cleared by ciliary activity and by coughing within 4 days. Some of this tantalum was swallowed and excreted. The tantalum reaching the gastrointestinal tract produced no untoward effects. Thus it was found that tantalum in the conducting airways was completely eliminated without significant inflammatory effects or absorption. Tantalum delivered to peripheral airways was cleared slowly via phagocytosis. During the phagocytic process, no evidence of fibroblastic or inflammatory response in the pulmonary tissue was noted. Thus it was found that modes of lung clearance of tantalum depend on deposition. Neither airways nor lung parenchyma showed adverse responses to tantalum.
Executive summary:

An experimental study was performed to determine the fate and metabolism of inhaled tantalum to dogs. During the study, dogs were insufflated with powdered tantalum and its retention and clearance monitored with bronchograms and roentgenograms.

Under the conditions of the study, tantalum was not found to cause unfavourable tissue reaction. When inhaled, there was no evidence of either acute or chronic inflammatory response in the airways or pulmonary tissue. Powdered tantalum delivered to the large airways was carried up the airways and cleared by ciliary activity and by coughing within 4 days. Some of this tantalum was swallowed and excreted. The tantalum reaching the gastrointestinal tract produced no untoward effects.

Thus it was found that tantalum in the conducting airways was completely eliminated without significant inflammatory effects or absorption. Tantalum delivered to peripheral airways was cleared slowly via phagocytosis. During the phagocytic process, no evidence of fibroblastic or inflammatory response in the pulmonary tissue was noted. Thus it was found that modes of lung clearance of tantalum depend on deposition. Neither airways nor lung parenchyma showed adverse responses to tantalum.