Divanadium pentaoxide

Specific investigations: other studies

Administrative data

Endpoint:

nephrotoxicity

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: Well reported study. Varying numbers of animals reported for different parameters have only a small impact on the reliability of the study.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Vanadium, Na-K-ATPase, and potassium adaptation in the rat.

Author:

Higashino, H.; et al.

Year:

1983

Bibliographic source:

American journal of physiology, 244, F105-11

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

A subacute study on the influence of oral vanadate on kidney function was described. Six groups of rats received either a diet normal with respect to Na and K content or a diet with a challenging high concentration of K. In addition, the groups received 0, 5 or 25 ppm NaVO3 in the diet for 2 weeks. Each animal was kept in a metabolic cage and weighed twice a week. On day 15, blood (plasma) and the following organs were taken from the animals for analytical and biochemical determinations: kidneys, liver, brain, distal segment of colon. V levels were determined.

GLP compliance:

not specified

Type of method:

in vivo

Endpoint addressed:

repeated dose toxicity: oral

Test material

Test material information

Constituent 1

Reference substance name:

Sodium metavanadate

IUPAC Name:

Sodium metavanadate

Constituent 2

Reference substance name:

Sodium metavanadate

EC Number:

237-272-7

EC Name:

Sodium metavanadate

Cas Number:

13718-26-8

Molecular formula:

NaVO3

IUPAC Name:

237-272-7

Constituent 3

Reference substance name:

13718-26-8

Cas Number:

13718-26-8

IUPAC Name:

13718-26-8

Details on test material:

- Name of test material (as cited in study report): sodium metavanadate
- Molecular formula (if other than submission substance): NaVO3
- Substance type: technical product
No further information given.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 170-200 g
- Housing: metabolic cages, single
- Diet: basal diet (0.08 ppm V) and either normal Na/K content or high K content
- Water: deionised water ad libitum
- Acclimation period: 1 week in metabolic cages
No further information given.

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: diet

Details on exposure:

DIET PREPARATION
- Different diets were prepared for the various exposure groups.
- Diet normal with respect to Na an K content (3 NK groups: 0.1 meq Na and 0.13 meq K/g food) was prepared and 0, 5 or 25 ppm NaVO3 were added.
- Diet with a challenging high concentration of K (3 HK groups: 0.1 meq Na and 1.82 meq K/g food) was prepared and 0, 5 or 25 ppm NaVO3 were added.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

V contents were measured in the basal diet and was found to be 0.08 ppm.

Duration of treatment / exposure:

2 weeks

Frequency of treatment:

continuously (in diet)

Post exposure period:

none

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
5 ppm NaVO3
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
25 ppm NaVO3
Basis:
nominal in diet

No. of animals per sex per dose:

six groups of 8 females

Control animals:

yes, plain diet

Details on study design:

- Each animal was kept in a metabolic cage.
- Rats were randomly assigned to exposure groups.

Examinations

Examinations:

- Each animal was weighed twice a week.
- Intake of solid food was measuered daily.
- After the two weeks of exposure, two consecutive 24 h urine samples were taken in the 0 and 25 ppm V exposure groups for determining endogenous creatine and Na and K fractional excretion.
- After 2 weeks of exposure on day 15, animals were anesthetized, blood (plasma) and the following organs were taken for analytical and biochemical determinations: kidneys, liver, brain, distal segment of colon. V levels were determined by a modified AAS method.

Positive control:

no data

Results and discussion

Details on results:

- V content in the basal diet was determined to be 0.08 ppm. Uptake of V in the diet was found to be proportional to the V content in the diet.
- Animals of the high dose V groups frequently developed diarrhoe 2 days following start of the exposure. Diarrhoe subsided after some days.
- Body weight gain was reduced in the HK groups whereas V had no influence on body weight gain.
- Vanadate supplemtation did not affect food intake.
- Fluid uptake was much higher in the HK groups demonstrating polyuria, presumably due to increased osmotic pressure.
- V content in various tissues was found positively correlated to the V content in the diet.
- The highest V conc. were found in the kidney and the lowest in the brain. These conc. were higher than the IC-50 of ATPase acitivities in vitro determined in previous studies.
- Detectable amounts of V were found only in the liver, renal cortex and plasma of groups not exposed to V.
- K had no influence on V uptake or distribution.
- Haematocrit values did not differ among the groups (data not shown).
- Plasma concentration of Na and K did not differ in all 6 groups.
- The profiles of Na-K-ATPase specific activities in various organs were as follows: renal medulla>brain>renal cortex>distal colon>>liver. In HK groups, a rise in the activities were found in the renal cortex, renal medulla and colon. V treatment did not influence Na-K-ATPase activities.
- High V or K intake did not alter creatinine clearance.
- Fractional excretion of K was enhanced proportional to the K load in NK and HK groups irrespective of V exposure.

Any other information on results incl. tables

Vandadium intakes:

Control groups: NK group = 6.5 ±0.3 meq/kg bw*d; HK group = 6.7±0.3 meq/kg bw*d

5 ppm groups: NK group = 452.7±18.4 meq/kg bw*d; HK group = 462.8±6.5 meq/kg bw*d

25 ppm groups: NK group = 2129.5±91.2 meq/kg bw*d; HK group = 2223.1±90.5 meq/kg bw*d

Applicant's summary and conclusion

Conclusions:

The study demonstrates that subacute oral exposure to V(5+) does not inhibit adaption to a markedly increased subacute K load refuting thereby previous hypotheses on the inhibition of Na-K-ATPase and an impairment of renal functions by a high oral exposure of V in vivo.