Cerium vanadium tetraoxide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: only abstract available.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

The fate of intragastrically or intratracheally administered or inhaled vanadium-48 oxydichloride in juvenile and mature rats

Author:

Sollenberger, D.M.

Year:

1982

Bibliographic source:

Dissertation Abstracts International, 42 (8): 3176-B.

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The objective of this research was to investigate the absorption of soluble vanadium (vanadium oxydichloride) from the respiratory tract of male Sprague Dawley rats of two ages.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

vanadium dichloride oxide

IUPAC Name:

vanadium dichloride oxide

Constituent 2

Reference substance name:

Vanadium dichloride oxide

EC Number:

233-517-7

EC Name:

Vanadium dichloride oxide

IUPAC Name:

233-517-7

Constituent 3

Reference substance name:

10213-09-9

Cas Number:

10213-09-9

IUPAC Name:

10213-09-9

Details on test material:

- Name of test material (as cited in study report): Vanadium oxydichloride (labelled with vanadium-48)
No further information on the test material was stated.

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Juvenile and mature rats
- Individual metabolism cages: yes
No further information on the test animals was stated.

Administration / exposure

Route of administration:

intratracheal

Vehicle:

not specified

Details on exposure:

A group of 10 rats were administered vanadium oxydichloride (labeled with vanadium-48) by intratracheal injection. Six replicates of the administration mode were performed. The average deposition in the respiratory tract was 1.0 +/- 0.1 µg (5.3 +/- 0.4 µCi) vanadium for the intratracheal injections. The activity median aerodynamic diameter, AMA, for the aerosol exposures averaged 0.76 microns with a geometric standard deviation of 1.96.
No further information on the exposure was stated.

Duration and frequency of treatment / exposure:

Six replicates of the administration mode were performed.

Doses / concentrations

Remarks:

Doses / Concentrations:
The average deposition in the respiratory tract was 1.0 +/- 0.1 µg (5.3 +/- 0.4 µCi) vanadium for the intratracheal injections. The activity median aerodynamic diameter, AMA, for the aerosol exposures averaged 0.76 microns with a geometric standard deviation of 1.96.

No. of animals per sex per dose / concentration:

5 juvenile male rats and 5 mature male rats

Control animals:

not specified

Positive control reference chemical:

No data

Details on study design:

No data

Details on dosing and sampling:

Immediately following vanadium administration, the animals were placed in individual metabolism cages enabling collection of the urine and feces.
The animals were sacrificed at various times, 1/2, 2, 6, 24, or 96 hours post administration, and selected organs and tissues were removed and analyzed for their vanadium-48 content. The amount of vanadium-48 was determined using a large well NaI(TI) crystal detection system.
The urine and fecal values were used as indicators of systemic (absorbed) and unabsorbed vanadium, respectively.
No further information on the dosing and sampling was stated.

Statistics:

No data

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

The absorption from the lungs following intratracheal injection was rapid with approximately 51 % of the administered dose remaining in the lungs at 30 minutes and 8.6 % remaining at 4 days.

Main ADME results 2

Results:

The urine and fecal values were used as indicators of systemic (absorbed) and unabsorbed vanadium, respectively. From this study, an absorption value of 80 % from the lungs has been calculated.

Main ADME results 3

Results:

In intratracheal injection mode of administration, the mature animals retained a larger percentage (8.5%) of the administered dose in the lungs than the juvenile animals (3.7%).

Main ADME results 4

Results:

The juvenile animals initially had higher levels in the spleen than the mature animals but this difference disappeared at 4 days. The juvenile animals consistently had femur vanadium levels that were 50 to 100% above those in the mature animals.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The absorption from the lungs following intratracheal injection was rapid with approximately 51 % of the administered dose remaining in the lungs at 30 minutes and 8.6 % remaining at 4 days. The 0.76 micron AMAD aerosol generated for the inhalation administration favored deposition in the lungs and nasopharyngeal regions of the respiratory tract.
The urine and fecal values were used as indicators of systemic (absorbed) and unabsorbed vanadium, respectively. From this study, an absorption value of 80 % from the lungs has been calculated.
In intratracheal injection mode of administration, the mature animals retained a larger percentage (8.5%) of the administered dose in the lungs than the juvenile animals (3.7%). The juvenile animals initially had higher levels in the spleen but this difference disappeared at 4 days. The juvenile animals consistently had femur vanadium levels that were 50 to 100% above those in the mature animals. All other Tissues and excreta did not show differences attributable to the age of the experimental animals.

Details on distribution in tissues:

No data

Details on excretion:

No data

Metabolite characterisation studies

Metabolites identified:

not specified

Details on metabolites:

No data

Applicant's summary and conclusion

Conclusions:

The absorption from the lungs following intratracheal injection was rapid with approximately 51 % of the administered dose remaining in the lungs at 30 minutes and 8.6 % remaining at 4 days. The 0.76 micron AMAD aerosol generated for the inhalation administration favored deposition in the lungs and nasopharyngeal regions of the respiratory tract.
The urine and fecal values were used as indicators of systemic (absorbed) and unabsorbed vanadium, respectively. From this study, an absorption value of 80 % from the lungs has been calculated.
In intratracheal injection mode of administration, the mature animals retained a larger percentage (8.5%) of the administered dose in the lungs than the juvenile animals (3.7%). The juvenile animals initially had higher levels in the spleen but this difference disappeared at 4 days. The juvenile animals consistently had femur vanadium levels that were 50 to 100% above those in the mature animals. All other tissues and excreta did not show differences attributable to the age of the experimental animals.