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Acute toxicity of vanadium compounds in rats and mice
227
Toxicology Letters, 23 (1984) 227-231 Elsevier
TOXLett. 1311
ACUTE TOXICITY
OF VANADIUM
(Sodium metavanadate;
COMPOUNDS
IN EATS AND MICE
vanadyl sulphate; single dose; LDso calculations)
J.M. LLOBET and J.L. DOMINGO Department of Biochemistry, Faculty of Medicine, University of Barcelona, C/. San Llorenc., 21, Reus (Spain) (Received June 4th, 1984) (Revision received July 23rd, 1984) (Accepted July 26th, 1984)
SUMMARY Sodium metavanadate (NaVOr) and vanadyl sulphate pentahydrate (VOSO4 . 5HrO) were administered to rats and mice. The following LDso (14-day) were determined: NaVOs, 98.0 mg/kg (rats) and 74.6 mg/kg (mice) when given orally, and 18.4 mg/kg (rats) and 35.9 mg/kg (mice) when given i.p.; VOSO4 . 5H20, 448.0 mg/kg (rats) and 467.2 mg/kg (mice) when given orally, and 74.1 mg/kg (rats) and 113.0 mg/kg (mice) when given i.p. The majority of deaths occurred during the first 24 h. The clinical and physical signs appearing after the intoxication include irregular respiration, diarrhea, ataxia and paralysis of the hind legs. These signs disappeared for the most part after 48 h, which suggests a quick elimination of vanadium.
INTRODUCTION
It is a well known fact that vanadium consitutes grave risks to health. Conjunctivitis, pharyngitis, rhinitis, chronic productive cough and tightness of the chest have been reported [l , 21. On the other hand, vanadium compounds have attracted the investigators’ interest due to their possible role in cellular regulation, with profound effects on enzymes of plasma membranes [3]. Orthovanadate has been found to be an inhibitor of (Na+ -K+)ATPase from kidney, red blood cells, skeletal muscle and heart [4-61 as potent as cardiac glycosides giving 50% inhibition at 40 nM [7]. However, there is little information on the acute toxicity of vanadium compounds in animals. The reports published refer to different compounds, species of animals and ways of administration [S-lo]. To combine this information, the acute toxicities from two vanadium compounds, NaVO3 with pentavalent vanadium and VOSO4 with tetravalent vanadium, have been determined in this paper. Both compounds were given orally and i.p. to rats and mice in a single dose. 0378-4274/84/$ 03.00 0 Elsevier Science Publishers B.V.
228
METHODS
NaV03, VOSO4 - SH20, and Tris, tris(hydroxymethyl)-amino-methane of analytical grade, were obtained from Merck (Darmstadt, FRG). Vanadium compounds were given orally and i.p. to male Sprague-Dawley rats weighing 200-250 g, and male Swiss mice weighing 25-30 g. In both cases 10 animals in each group were used. The animals were supplied by Biocentre (Barcelona, Spain) and had free access to food (Panlab diet) and water. NaVOs and VOSO4 were dissolved in 10 mM Tris-HCl-NaC1 buffer (pH 7.4). Oral doses were given intragastrically. Solution concentrations were adjusted so that a 250-g rat received 1 ml and a 30-g mouse 0.2 ml. To calculate the LDso values, a preceding screening with small groups of two or three animals of each kind was carried out. The treated animals were observed for 14 days. Groups of control animals received Tris-Hcl-NaCl buffer (pH 7.4). The LDso values for rats and mice were calculated according to the Litchfield and Wilcoxon method [ 111. RESULTS
LDSO calculations Tables I and II summarize the relation between dosage and mortality in rats and mice, respectively, when vanadium compounds were given orally and i.p. LDso values (14-days) and their 95% confidence limits are also shown.
TABLE
I
ACUTE
TOXICITY
OF VANADIUM
COMPOUNDS
IN RATS
VOSOs .5HzO
NaVO3 Oral administration
1.~. administration
Oral administration
1.~. administration
Dose
Alive/
Dose
Alive/
Dose
Alive/
Dose
Alive/
(mg/kg)
Tested
(mg/kg)
Tested
(mg/kg)
Tested
(mg/kg)
Tested
39 62
lO/lO 8/10
7 10
lO/lO 9/10
296 395
lO/lO 6110
50 65
lO/lO 7/10
100
6/10
15
4/10
500
4/10
85
3/10
160
2/10
23
2/10
650
3/10
110
2/10
256
o/10
LDso of NaVO3:
34 O/10 LDso of NaVO3:
845 o/10 LD5o of VOSO4.5H20:
98.0 (127.4, 75.4) LDsOfor V + ‘:
18.4 (22.6, 14.9) LD5o for V+5:
448.0 (486.9, LD5o for V+4:
7.7 (9.4, 6.2)’
90.3 (98.1,
41.0 (53.3, 31.5)a LDSO (14-days)
in mg/kg;
95% confidence
limits in parentheses.
412.2)
83.1)” a calculated.
143 O/10 LDs,, of VOSOd .
5&o:
74.1 (87.1, 63.0) LD5o for V+4 14.9 (17.6, 12.7)a
229 TABLE II ACUTE TOXICITY OF VANADIUM COMPOUNDS IN MICE VOSO‘, .5HzO
NaVO, Oral administration
1.~. administration
Oral administration
1.~. administration
Dose (mg/kg)
Alive/ Tested
Dose (mg/kg)
Alive/ Tested
Dose (mg/kg)
Alive/ Tested
Dose (mg/kg)
Alive/ Tested
41 57 80 113 157
IO/IO 7110 4/10 3/10 O/IO
18 27 40 61 91
IO/IO 6110 4/10 3/10 O/IO
186 260 364 510 714
lO/lO 8110 8/10 3/10 O/10
45 64 90 127 178
10110 9110 7/10 4/10 O/IO
LDsa of NaV03: 74.6 (100.7, 55.3) LDso for V +s 31.2 (42.1, 23.1)=
LDsc of NaVOs: 35.9 (51.3, 25.1) LDsc for V+5: 15.0 (21.4, 10.5)a
LDso of VOSO4.5HzO: 467.2 (608.7, 359.4) LDso for V +4.. 94.2 (122.8, 72.4)a
LDso (14 day) in mg/kg; 95% confidence limits in parentheses.
LDso VOSO4.5HzO: 113.0 (149.2, 85.6) LDso for V+‘4: 22.8 (30.1, 17.3)a
a Calculated.
Physical and clinical observations In the case of oral administration, the majority of deaths were observed (in both species and vanadium compounds) within the first 48 h. Few deaths occurred betwen the second and the seventh days. No death occurred after 7 days. In the case of i.p. administration deaths occurred immediately in animals which received the highest
TABLE III SEVERITY OF PHYSICAL AND CLINICAL SIGNS IN RATS AND MICE AFTER VANADIUM ADMINISTRATION IN A SINGLE DOSE Number of days after vanadium administration 1
2
3-7
8-14
Mortality rate? Oral 1.p.
60% 80%
30% 20%
10% 0%
0% 0%
Diarrheab
+++
+++
+
none
+++
+
none
none
+++
++
+
none
Irregular respiration, rhythm, ataxia
increased cardiac
Decreased locomotor activity, paralysis of the hind legs, decreased sensitivity to pain
‘The mortality rates are averages for both species and vanadium compounds. bDiarrhea was only observed in rats. + , light; + + , moderate; + + + , severe symptomatology.
230
doses. The highest mortality rates occurred within the first 24 h. No death occurred after 48 h. The highest dosages of both vanadium compounds caused intense diarrhea, irregular respiration, increased cardiac rhythm and ataxia. These disturbances were more noticeable in rats treated with NaVO3. No diarrhea was observed in the case of mice. The most noticeable physical signs observed were: decreased locomotor activity, paralysis of the hind legs and decreased sensivity to pain. Most clinical and physical signs appeared within 24 h, and most of them disappeared 48 h after the administration of the vanadium compounds (Table III). DISCUSSION
From the results obtained, it can be seen that NaVO3 was highly toxic when given i.p. to rats and mice. NaVO3, when given orally, was moderately toxic. VOSO4 was moderately toxic when given orally and i.p. to both species. Calculated on the basis of the vanadium ions, the acute toxicities of both vanadium compounds tested were higher for rats than for mice, with the exception of NaVO3 when given orally. The toxicity increases as the valence increases, as it has already been described 1121. The fact that the acute oral toxicity of vanadium compounds was much lower than the acute i.p, toxicity was thought to be due to a low rate of absorption. Vanadium salts are poorly absorbed from the intestine [ 131. Nevertheless, our results are not in agreement with those of Stokinger [8], who mentioned a low toxicity when vanadium was administered orally. We have obtained LDso values for NaV03, which allow us to consider a moderate toxicity for this compound when given orally. In view of these disagreements, it can be interesting in a future research to determine the vanadium concentration in different organs after a single dose of vanadium. It would allow us to assess the rate of absorption. The physical and clinical signs practically disappeared between 24 and 72 h, which suggests a quick elimination of vanadium [14, 1.51. This is corroborated by the absence of deaths after 72 h. On the other hand, the symptoms could indicate that vanadium in acutely fatal doses acts mainly in the central nervous system [16]. Nevertheless, another important possible cause of death may be the fact that vanadium compounds inhibit a large number of cellular activities, with profound effects on enzymes of plasma membranes [3, 171. REFERENCES 1 M.D. Waters, Toxicology of vanadium in R.A. Goyer and M.A. Mehlam (Ed%), Advances in Modern Toxicology, Wiley, New York, 1977, p. 147.
231
2 P.B. Hammond icology,
and R.P.
Beliles, Metals,
the Basic Science
3 T. Ramasarma, membrane,
W.C.
Biochim.
4 W.E. Balfour,
of Poisons,
MacKellan
Acta,
and 1.M. Glynn,
side, Nature,
ATPase
7 L.C. Cantley, a potent
Commercial
to external
L. Josephson,
Vanadate-stimulated
Vanadate-stimulated Vanadate
NADH
oxidation
natriuresis
inhibits
ATP containing
potassium,
Nature,
R. Warner,
(Na’-K+)ATPase
(Eds.),
Tox-
in plasma
in the at, Nature,
the red cell (Na+-K+)
ATPase
275 from
272 (1978) 552-554.
6 L.A. Beauge and I.M. Glynn, (Na+-K+)
and M.O. Amdur
1980, p. 460.
646 (1981) 88-98.
Jr., M.D. Resh and G. Guidotti,
the cytoplasmic
New York,
and F.L. Crane,
Biophys.
J.J. Grantham
(1978) 768. 5 L.C. Cantley
in J. Doull, C.D. Klaassen
Macmillan,
inhibitor
traces of vanadate
M. Yanagisawa,
found
alters the response
of
272 (1978) 551-552. C. Lechene
in ATP derived
and G. Guidotti,
from muscle,
Vanadate
J. Biol. Chem.,
is
252 (1977)
7421-7423. 8 H.E. Stokinger,
The metals (excluding
lead). Vanadium,
in F.A. Patty (Ed.), Industrial
Toxicology, Interscience, New York, 1963, pp. 1171-1182. 9 R.D.R. Parker and R.P. Sharma, Accumulation and depletion treated
with vanadyl
235-245. 10 M. Heide,
W.
demethylation
Legrum,
Sciences,
K.J.
and F. Wilcoxon,
Exp. Ther.,
12 Committee
and sodium Netter
orthovanadate,
and
in vivo in mice, Toxicology,
11 J.T. Litchfield macol.
sulphate
on
Fuhrmann,
and
in selected tissues of rats Pathol.
Vanadium
Toxicol.,
inhibits
2 (1978)
oxidative
drug
26 61983) 63-71.
A simplified
method
of evaluating
dose-effect
experiments.
J. Phar-
96 (1949) 99-113.
Biologic
Washington,
13 C. Zenz, Vanadium,
G.F.
of vanadium J. Environ.
Hygiene
Effects
of Atmospheric
Pollutants,
Vanadium,
National
Academy
of
DC, 1974, pp. 55-56. in H.A.
Waldron
(Ed.),
Metals in the Environment,
Academic
Press,
London,
1980, pp. 300-310. 14 N.A.
Talvitie
vanadium 15 N.L. gold,
and W.D.
in animals,
Wagner,
Studies
Am. Med. Assoc.
Kent and R.A.
McCance,
lithium,
and vanadium,
boron
16 C.I. Wei, M.A. ammonium
Al Bayati,
metavanadate
17 B.S. Jandhyala
M.R.
in vanadium Arch.
The absorption Biochem.
Culberston,
in mice, J. Toxicol.
and G.J. Horn, Physiological
33 (1983) 1325-1340.
toxicology,
Ind. Hyg.,
II. Distribution
and excretion
of
9 (1954) 414-422.
of excretion
of ‘minor’
elements
by man,
1. Silver,
J., 35 (1941) 837-844. L.S. Rosenblatt Environ.
Health,
and pharmacological
and L.D.
Hansen,
Acute
toxicity
of
10 (1982) 673-687. properties
of vanadium,
Life Sci.,
Toxicology Letters, 23 (1984) 227-231 Elsevier
TOXLett. 1311
ACUTE TOXICITY
OF VANADIUM
(Sodium metavanadate;
COMPOUNDS
IN EATS AND MICE
vanadyl sulphate; single dose; LDso calculations)
J.M. LLOBET and J.L. DOMINGO Department of Biochemistry, Faculty of Medicine, University of Barcelona, C/. San Llorenc., 21, Reus (Spain) (Received June 4th, 1984) (Revision received July 23rd, 1984) (Accepted July 26th, 1984)
SUMMARY Sodium metavanadate (NaVOr) and vanadyl sulphate pentahydrate (VOSO4 . 5HrO) were administered to rats and mice. The following LDso (14-day) were determined: NaVOs, 98.0 mg/kg (rats) and 74.6 mg/kg (mice) when given orally, and 18.4 mg/kg (rats) and 35.9 mg/kg (mice) when given i.p.; VOSO4 . 5H20, 448.0 mg/kg (rats) and 467.2 mg/kg (mice) when given orally, and 74.1 mg/kg (rats) and 113.0 mg/kg (mice) when given i.p. The majority of deaths occurred during the first 24 h. The clinical and physical signs appearing after the intoxication include irregular respiration, diarrhea, ataxia and paralysis of the hind legs. These signs disappeared for the most part after 48 h, which suggests a quick elimination of vanadium.
INTRODUCTION
It is a well known fact that vanadium consitutes grave risks to health. Conjunctivitis, pharyngitis, rhinitis, chronic productive cough and tightness of the chest have been reported [l , 21. On the other hand, vanadium compounds have attracted the investigators’ interest due to their possible role in cellular regulation, with profound effects on enzymes of plasma membranes [3]. Orthovanadate has been found to be an inhibitor of (Na+ -K+)ATPase from kidney, red blood cells, skeletal muscle and heart [4-61 as potent as cardiac glycosides giving 50% inhibition at 40 nM [7]. However, there is little information on the acute toxicity of vanadium compounds in animals. The reports published refer to different compounds, species of animals and ways of administration [S-lo]. To combine this information, the acute toxicities from two vanadium compounds, NaVO3 with pentavalent vanadium and VOSO4 with tetravalent vanadium, have been determined in this paper. Both compounds were given orally and i.p. to rats and mice in a single dose. 0378-4274/84/$ 03.00 0 Elsevier Science Publishers B.V.
228
METHODS
NaV03, VOSO4 - SH20, and Tris, tris(hydroxymethyl)-amino-methane of analytical grade, were obtained from Merck (Darmstadt, FRG). Vanadium compounds were given orally and i.p. to male Sprague-Dawley rats weighing 200-250 g, and male Swiss mice weighing 25-30 g. In both cases 10 animals in each group were used. The animals were supplied by Biocentre (Barcelona, Spain) and had free access to food (Panlab diet) and water. NaVOs and VOSO4 were dissolved in 10 mM Tris-HCl-NaC1 buffer (pH 7.4). Oral doses were given intragastrically. Solution concentrations were adjusted so that a 250-g rat received 1 ml and a 30-g mouse 0.2 ml. To calculate the LDso values, a preceding screening with small groups of two or three animals of each kind was carried out. The treated animals were observed for 14 days. Groups of control animals received Tris-Hcl-NaCl buffer (pH 7.4). The LDso values for rats and mice were calculated according to the Litchfield and Wilcoxon method [ 111. RESULTS
LDSO calculations Tables I and II summarize the relation between dosage and mortality in rats and mice, respectively, when vanadium compounds were given orally and i.p. LDso values (14-days) and their 95% confidence limits are also shown.
TABLE
I
ACUTE
TOXICITY
OF VANADIUM
COMPOUNDS
IN RATS
VOSOs .5HzO
NaVO3 Oral administration
1.~. administration
Oral administration
1.~. administration
Dose
Alive/
Dose
Alive/
Dose
Alive/
Dose
Alive/
(mg/kg)
Tested
(mg/kg)
Tested
(mg/kg)
Tested
(mg/kg)
Tested
39 62
lO/lO 8/10
7 10
lO/lO 9/10
296 395
lO/lO 6110
50 65
lO/lO 7/10
100
6/10
15
4/10
500
4/10
85
3/10
160
2/10
23
2/10
650
3/10
110
2/10
256
o/10
LDso of NaVO3:
34 O/10 LDso of NaVO3:
845 o/10 LD5o of VOSO4.5H20:
98.0 (127.4, 75.4) LDsOfor V + ‘:
18.4 (22.6, 14.9) LD5o for V+5:
448.0 (486.9, LD5o for V+4:
7.7 (9.4, 6.2)’
90.3 (98.1,
41.0 (53.3, 31.5)a LDSO (14-days)
in mg/kg;
95% confidence
limits in parentheses.
412.2)
83.1)” a calculated.
143 O/10 LDs,, of VOSOd .
5&o:
74.1 (87.1, 63.0) LD5o for V+4 14.9 (17.6, 12.7)a
229 TABLE II ACUTE TOXICITY OF VANADIUM COMPOUNDS IN MICE VOSO‘, .5HzO
NaVO, Oral administration
1.~. administration
Oral administration
1.~. administration
Dose (mg/kg)
Alive/ Tested
Dose (mg/kg)
Alive/ Tested
Dose (mg/kg)
Alive/ Tested
Dose (mg/kg)
Alive/ Tested
41 57 80 113 157
IO/IO 7110 4/10 3/10 O/IO
18 27 40 61 91
IO/IO 6110 4/10 3/10 O/IO
186 260 364 510 714
lO/lO 8110 8/10 3/10 O/10
45 64 90 127 178
10110 9110 7/10 4/10 O/IO
LDsa of NaV03: 74.6 (100.7, 55.3) LDso for V +s 31.2 (42.1, 23.1)=
LDsc of NaVOs: 35.9 (51.3, 25.1) LDsc for V+5: 15.0 (21.4, 10.5)a
LDso of VOSO4.5HzO: 467.2 (608.7, 359.4) LDso for V +4.. 94.2 (122.8, 72.4)a
LDso (14 day) in mg/kg; 95% confidence limits in parentheses.
LDso VOSO4.5HzO: 113.0 (149.2, 85.6) LDso for V+‘4: 22.8 (30.1, 17.3)a
a Calculated.
Physical and clinical observations In the case of oral administration, the majority of deaths were observed (in both species and vanadium compounds) within the first 48 h. Few deaths occurred betwen the second and the seventh days. No death occurred after 7 days. In the case of i.p. administration deaths occurred immediately in animals which received the highest
TABLE III SEVERITY OF PHYSICAL AND CLINICAL SIGNS IN RATS AND MICE AFTER VANADIUM ADMINISTRATION IN A SINGLE DOSE Number of days after vanadium administration 1
2
3-7
8-14
Mortality rate? Oral 1.p.
60% 80%
30% 20%
10% 0%
0% 0%
Diarrheab
+++
+++
+
none
+++
+
none
none
+++
++
+
none
Irregular respiration, rhythm, ataxia
increased cardiac
Decreased locomotor activity, paralysis of the hind legs, decreased sensitivity to pain
‘The mortality rates are averages for both species and vanadium compounds. bDiarrhea was only observed in rats. + , light; + + , moderate; + + + , severe symptomatology.
230
doses. The highest mortality rates occurred within the first 24 h. No death occurred after 48 h. The highest dosages of both vanadium compounds caused intense diarrhea, irregular respiration, increased cardiac rhythm and ataxia. These disturbances were more noticeable in rats treated with NaVO3. No diarrhea was observed in the case of mice. The most noticeable physical signs observed were: decreased locomotor activity, paralysis of the hind legs and decreased sensivity to pain. Most clinical and physical signs appeared within 24 h, and most of them disappeared 48 h after the administration of the vanadium compounds (Table III). DISCUSSION
From the results obtained, it can be seen that NaVO3 was highly toxic when given i.p. to rats and mice. NaVO3, when given orally, was moderately toxic. VOSO4 was moderately toxic when given orally and i.p. to both species. Calculated on the basis of the vanadium ions, the acute toxicities of both vanadium compounds tested were higher for rats than for mice, with the exception of NaVO3 when given orally. The toxicity increases as the valence increases, as it has already been described 1121. The fact that the acute oral toxicity of vanadium compounds was much lower than the acute i.p, toxicity was thought to be due to a low rate of absorption. Vanadium salts are poorly absorbed from the intestine [ 131. Nevertheless, our results are not in agreement with those of Stokinger [8], who mentioned a low toxicity when vanadium was administered orally. We have obtained LDso values for NaV03, which allow us to consider a moderate toxicity for this compound when given orally. In view of these disagreements, it can be interesting in a future research to determine the vanadium concentration in different organs after a single dose of vanadium. It would allow us to assess the rate of absorption. The physical and clinical signs practically disappeared between 24 and 72 h, which suggests a quick elimination of vanadium [14, 1.51. This is corroborated by the absence of deaths after 72 h. On the other hand, the symptoms could indicate that vanadium in acutely fatal doses acts mainly in the central nervous system [16]. Nevertheless, another important possible cause of death may be the fact that vanadium compounds inhibit a large number of cellular activities, with profound effects on enzymes of plasma membranes [3, 171. REFERENCES 1 M.D. Waters, Toxicology of vanadium in R.A. Goyer and M.A. Mehlam (Ed%), Advances in Modern Toxicology, Wiley, New York, 1977, p. 147.
231
2 P.B. Hammond icology,
and R.P.
Beliles, Metals,
the Basic Science
3 T. Ramasarma, membrane,
W.C.
Biochim.
4 W.E. Balfour,
of Poisons,
MacKellan
Acta,
and 1.M. Glynn,
side, Nature,
ATPase
7 L.C. Cantley, a potent
Commercial
to external
L. Josephson,
Vanadate-stimulated
Vanadate-stimulated Vanadate
NADH
oxidation
natriuresis
inhibits
ATP containing
potassium,
Nature,
R. Warner,
(Na’-K+)ATPase
(Eds.),
Tox-
in plasma
in the at, Nature,
the red cell (Na+-K+)
ATPase
275 from
272 (1978) 552-554.
6 L.A. Beauge and I.M. Glynn, (Na+-K+)
and M.O. Amdur
1980, p. 460.
646 (1981) 88-98.
Jr., M.D. Resh and G. Guidotti,
the cytoplasmic
New York,
and F.L. Crane,
Biophys.
J.J. Grantham
(1978) 768. 5 L.C. Cantley
in J. Doull, C.D. Klaassen
Macmillan,
inhibitor
traces of vanadate
M. Yanagisawa,
found
alters the response
of
272 (1978) 551-552. C. Lechene
in ATP derived
and G. Guidotti,
from muscle,
Vanadate
J. Biol. Chem.,
is
252 (1977)
7421-7423. 8 H.E. Stokinger,
The metals (excluding
lead). Vanadium,
in F.A. Patty (Ed.), Industrial
Toxicology, Interscience, New York, 1963, pp. 1171-1182. 9 R.D.R. Parker and R.P. Sharma, Accumulation and depletion treated
with vanadyl
235-245. 10 M. Heide,
W.
demethylation
Legrum,
Sciences,
K.J.
and F. Wilcoxon,
Exp. Ther.,
12 Committee
and sodium Netter
orthovanadate,
and
in vivo in mice, Toxicology,
11 J.T. Litchfield macol.
sulphate
on
Fuhrmann,
and
in selected tissues of rats Pathol.
Vanadium
Toxicol.,
inhibits
2 (1978)
oxidative
drug
26 61983) 63-71.
A simplified
method
of evaluating
dose-effect
experiments.
J. Phar-
96 (1949) 99-113.
Biologic
Washington,
13 C. Zenz, Vanadium,
G.F.
of vanadium J. Environ.
Hygiene
Effects
of Atmospheric
Pollutants,
Vanadium,
National
Academy
of
DC, 1974, pp. 55-56. in H.A.
Waldron
(Ed.),
Metals in the Environment,
Academic
Press,
London,
1980, pp. 300-310. 14 N.A.
Talvitie
vanadium 15 N.L. gold,
and W.D.
in animals,
Wagner,
Studies
Am. Med. Assoc.
Kent and R.A.
McCance,
lithium,
and vanadium,
boron
16 C.I. Wei, M.A. ammonium
Al Bayati,
metavanadate
17 B.S. Jandhyala
M.R.
in vanadium Arch.
The absorption Biochem.
Culberston,
in mice, J. Toxicol.
and G.J. Horn, Physiological
33 (1983) 1325-1340.
toxicology,
Ind. Hyg.,
II. Distribution
and excretion
of
9 (1954) 414-422.
of excretion
of ‘minor’
elements
by man,
1. Silver,
J., 35 (1941) 837-844. L.S. Rosenblatt Environ.
Health,
and pharmacological
and L.D.
Hansen,
Acute
toxicity
of
10 (1982) 673-687. properties
of vanadium,
Life Sci.,