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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: only 24 h urinary excretion considered for result

Data source

Reference
Reference Type:
publication
Title:
Distribution of vanadate in the rat following subcutaneous and oral routes of administration
Author:
Al-Bayati, M.A. et al.
Year:
1991
Bibliographic source:
Journal of the American College of Toxicology, 10 (2): 233 - 241.

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The distribution of radiolabeled vanadate (48V) was studied in rats following the oral route of administration (1.8 mg V/kg). Measurements included: (1) tissue uptake and retention; (2) gastrointestinal (GI) absorption efficiency; and (3) the fraction of the dose eliminated via the urinary and the GI tracts during the study period.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): Ammonium metavanadate
No further information on the test material was stated.
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS (Animals were chronic respiratory disease-free rats.)
- Source: Charles River (Wilmington, MA)
- Age at study initiation: 10 -11 weeks of age
- Housing: Immediately after treatment, the animals were placed individually in stainless steel metabolic cages.
- Individual metabolism cages: yes
- Diet (ad libitum): Rat chow
- Water (ad libitum): Acidified water (pH 6.0; the acidified water was prepared by adding 0.42 ml of 12 N HCl and 0.26 ml Clorox bleach to 1 L of water)
- Quarantine period: 2 weeks prior to treatment

ENVIRONMENTAL CONDITIONS
- Temperature: Approximately 25.6 °C
No further information on the test animals was stated.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
Radioactive 48V was supplied as carrier-free vanadyl chloride in 1 M HCl by Amersham, Inc., Arlington Heights, IL (specific activity = 2mCi/ml). It has a half-life of 16 days, decays by positron emission (Emnx = 0.70 MeV), and emits four gamma photons between 0.5 and 2.2 MeV. The 48V as vanadyl chloride was diluted to proper specific activity and neutralized with sodium hydroxide to pH 7.6 to yield vanadate. The carrier ammonium metavanadate powder, purity > 99 % (J.T. Baker Chemical Co., Phillipsburg, NJ), was dissolved in distilled and deionized water by stirring. The 48V solution was added to the ammonium vanadate solution. This mixture had a final pH of 7.6, vanadium concentration of 0.01 M, and specific activity of 1.62 µCi/ml. The solution was filtered through 0.2 µm pore disposable filter (Sybron Corp., Rochester, NY) and kept at room temperature until the time of treatment.
Vanadium dosage was determined by subtracting the 48V activity in the syringes and the tubes after the injection from the activity prior to injection.

Rats were restrained and the solution was injected into the stomach through a stomach tube. The tube was inserted into the mouth of the animal over the dorsal surface of the tongue and pushed gently backward through the oral pharynx and the esophagus to the stomach.
No further information on the exposure was stated.
Duration and frequency of treatment / exposure:
Administrated once
Doses / concentrations
Remarks:
Doses / Concentrations:
Dosage level of 1.8 mg V/kg (in 0.5 ml)
No. of animals per sex per dose:
36 male rats
Control animals:
yes
Positive control:
No data
Details on study design:
No data
Details on dosing and sampling:
- Excreta were collected daily.
- The treated animals were counted individually by gamma spectroscopy immediately following treatment and on the termination date to measure body burden of vanadium at various intervals of the study.
- Necropsy procedure: The animals were anesthetized with sodium pentothal (70 mg/kg i.p.), the chest cavity was opened and blood sample was obtained by cardiac puncture using a 6 ml disposable syringe and a 22 X 1.5 G needle. The major organs were carefully separated and were placed individually in preweighed container for determination of weight and radioactivity. The tissue samples included heart, thymus, spleen, lung, brain, submaxillary salivary glands, larynx and its tissue, trachea, esophagus, liver, kidneys, pancreas, stomach, small intestine, large intestine, testes, seminal vesicles, prostrate, urinary bladder and its contents, femur, abdominal fat, and carcass.
-Counting procedure: The 48V content of the whole rat, tissue, and excreta was measured by a gamma-ray counter equipped with sodium iodide crystals and a Nuclear Data ND66 multichannel analyzer (Nuclear Data, Inc., Roselle, IL). Each sample was placed in a container between NaI crystals and counted for 5- 10 minutes. Tissue from unexposed control rats and a known aliquot of 48V solution also were counted routinely for the same length of time to estimate background level and counting efficiency (14 - 28%), respectively. The sample size geometry was determined by counting a known aliquot of 48V solution in different volume of water (1-1000 ml). The net counts were corrected for isoope physical decay, counting efficiency, ansd sample size geometry.
No further information on dosing and sampling was stated.
Statistics:
The gastrointestinal uptake of gavaged vanadium during the first day was calculated.
The elimination half-life of vanadium in major organs was calculated.

Results and discussion

Preliminary studies:
No data
Main ADME resultsopen allclose all
Type:
absorption
Results:
A small fraction (4.2%) of the vanadium administered by gavage was absorbed from the GI tract during the first day.
Type:
distribution
Results:
The vanadium absorbed from the GI tract was distributed among major tissues (heart, lung, liver, kidney, carcass).
Type:
excretion
Results:
This study showed that most of the absorbed vanadium from the GI tract is excreted rapidly in urine.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
A small fraction (4.2%) of the vanadium administered by gavage was absorbed from the GI tract during the first day.
Details on distribution in tissues:
The vanadium absorbed from the GI tract was distributed among major tissues (heart, lung, liver, kidney, carcass).
Details on excretion:
This study showed that most of the absorbed vanadium from the GI tract is excreted rapidly in urine.

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
No data

Applicant's summary and conclusion

Conclusions:
Absorption: A small fraction (4.2%) of the vanadium administered by gavage was absorbed from the GI tract during the first day.
Distribution: The vanadium absorbed from the GI tract was distributed among major tissues (heart, lung, liver, kidney, carcass).
Excretion: This study showed that most of the absorbed vanadium from the GI tract is excreted rapidly in urine.