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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Specific investigations: other studies

Currently viewing:

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.