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Specific investigations: other studies

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Endpoint:
specific investigations: other studies
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: Reliable with restrictions. Experimental model.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Effects of chronic administration of vanadate on blood pressure, heart rate and Na+/K+-ATPase activity in adult male Wistar rats.
Author:
Jadhav, A.L.; Jandhyala, B.S.
Year:
1983
Bibliographic source:
Arch. Int. Pharmacodyn. 263, 74-84

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Five groups of male rats received either drinking water alone, water containing 20 mg/L Na3VO4 , 1% saline , 1% saline containing 20 mg/L NA3VO4 or water containing 200 mg/L NA3VO4 for a period of 6 weeks. Average daily intake of vanadate was determined. Cardiovascular effects of chronic vanadate consumption were investigated 6 weeks after exposure by determination of systolic blood pressure and heart rate, and pressor responses to norepinephrine (NE) and angiotensin II (A-II). In addition, renal Na+/K+-ATPase activity in kidney homogenates free of V were measured.
GLP compliance:
not specified
Type of method:
in vivo
Endpoint addressed:
repeated dose toxicity: oral

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): vanadate
- Molecular formula (if other than submission substance): Na3VO4
- Substance type: technical product
No further information given.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 200 and 250 g
- Diet: standard laboratory rat chow
- Water: different drinking fluids (see below "Details on exposure")
- Acclimation period: two weeks to acclimate to the procedure of measuring systolic blood pressure

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 °C
No further information given.

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
other: water or saline solution
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
- Group 1: drinking water alone
- Group 2: water containing 20 mg/L Na3VO4
- Group 3: 1% saline
- Group 4: 1% saline containing 20 mg/L NA3VO4
- Group 5: water containing 200 mg/L NA3VO4
No further information given.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
6 weeks
Frequency of treatment:
continuous (in drinking water)
Post exposure period:
no
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
20 mg/L Na3VO4 in water (group 2)
Basis:
nominal in water
Remarks:
Doses / Concentrations:
200 mg NA3VO4 /L in water (group 5)
Basis:
nominal in water
Remarks:
Doses / Concentrations:
20 mg/L Na3VO4 in 1% saline solution (group 4)
Basis:
other: nominal in saline
No. of animals per sex per dose:
8 rats per group
Control animals:
yes
Details on study design:
- Animals were randomly divided into 5 exposure groups.
- After the treatment period, the rats were anesthetized with urethane, i.p.

Examinations

Examinations:
- Average daily intake of vanadate was determined on the basis of fluid consumption per week.
- Cardiovascular effects of chronic vanadate consumption were investigated by weekly determination of systolic blood pressure and heart rate.
- Pressor responses to norepinephrine (NE) and angiotensin II (A-II) were determined after 6 weeks of exposure.
- In addition, renal Na+/K+-ATPase activity in kidney homogenates free of V was measured.
Positive control:
no data

Results and discussion

Details on results:
- Average daily intake of vanadate: group 1: 1.9 mg/kg bw/d; group 3: 3.2 mg/kg bw/d; group 5: 22.2 mg/kg bw/d.
- Changes in arterial pressure and variations of heart rate were essentially similar in all groups during the treatment period.
- At the end of 6 weeks, studies conducted under urethane anaesthesia showed that pressor responses to norepinephrine (NE) were potentiated in saline, saline + low vanadate and water + high vanadate groups when compared to that of water + low vanadate or drinking water groups.
- In all 3 groups in which NE responses were altered, renal Na+/K+-ATPase activity was significantly suppressed (25-35%).
- Pressor responses to angiotensin II (A-II) were significantly enhanced in all the groups receiving vanadate or saline when compared to that of the water group, and these changes occurred whether or not there was any change in renal Na+/K+-ATPase activity.
- Evidently, the changes noted in cardiovascular responses to vasoconstrictor agents are conducive to the development of high blood pressure.
- Failure to note sustained increase in arterial pressure during the treatment period may be due to the fact that in these rats renal compensation was not compromised.

Applicant's summary and conclusion

Conclusions:
In the current study, evidence was delivered that the cardiovascular system responded to vasoconstrictor agents in a dose-dependent manner after repeated oral vanadate exposure favouring the development of high blood pressure.