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Toxicological information

Specific investigations: other studies

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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

Constituent 1
Reference substance name:
Sodium metavanadate
IUPAC Name:
Sodium metavanadate
Constituent 2
Chemical structure
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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
5 ppm NaVO3
Basis:
nominal in diet
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.