Vanadyl pyrophosphate

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: 
Absorption via the oral and dermal routes is regarded as low. Absorption by the inhalation route is greater. Following absorption, vanadium is transported in the serum bound to transferrin and is distributed widely throughout the body. The highest amounts have been located in the bone, kidneys, liver, spleen and testes. Retention of vanadium has been reported, particularly in bone. Absorbed vanadium is predominantly excreted via urine. In humans initial clearance via urine is rapid, followed by a slower phase. About 60% of absorbed vanadium is excreted by the kidneys within 24 hours.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

Toxicokinetics

 

Absorption

In general, available data indicate that in both animals and humans, absorption of vanadium via the gastrointestinal tract is low.Vanadium in the vanadate (+5) state is absorbed about three to five times more effectively than in the vanadyl (+4) state (NTP,2008).Based on the poor absorption of vanadium from the GI tract, internal tissue concentrations and toxicity from oral exposure are expected to be low.Ingested vanadium is absorbed poorly by the gastrointestinal tract of humans. Only 0.1-1.0% of a 100 and 125 mg dose of diammonium oxytartarovanadate was absorbed gastrointestinally, and 60% of the absorbed dose was excreted by the kidneys within 24 hours (Curran et al, 1959). An oral dose of 0.3 mg/kg vanadium from vanadium pentoxide administered to rats resulted in only 2.6% being absorbed (Conklin et al, 1982). Wiegman et al studied the absorbtion and excretion of radioactive vanadium in rats. Vanadium was administered as sodium metavanadate by gavage (5μmol, corresponding to 0.255 mg vanadium). After 4 days, 18% of the dose was excreted in urine and 69% was recovered in the faeces. The remainder was retained in various organs and tissues. When A1(OH)₃gel was given to the rats at the same time as vanadium administration, aluminum hydroxide decreased the absorbtion of vanadium, 8% of the administered radioactivity being recovered in the urine and 86% recovered in the faeces.One study reported by Azay et al on the bioavailability of vanadium from vanadium sulphate after oral gavage administration of 7.5 and 15 mg vanadium/kg to rats indicates higher absorption, estimated to be 16.8 and 12.5 %, as determined from area under the curve (AUC) data compared with intravenous administration.

 

Dermal exposure is also reported to result in poor absorption (Janssen et al., 1998; EFSA, 2004; IARC, 2006).

 

Absorption of vanadium in the lungs following inhalation exposure is higher and depends on particle size and the solubility of the vanadium compound (Janssen et al., 1998).Conklin et al. (1982) reported that 100% of an intratracheal dose of 0.3 mg/kg vanadium administered as radiolabeled vanadium pentoxide was absorbed by rats. Approximately 40% of the recovered radioactivity had been cleared from the lungs within 1 hour, and 90% had been cleared within 3 days. Clearance from the lung was primarily into blood, liver and bone, indicating rapid absorption. By post-treatment day 3, 40% of the radioactivity had been recovered in the urine. Similar results were obtained for vanadyl chloride.

 

Distribution

Following oral uptake in rats, vanadium is transported in the serum bound to transferrin and is distributed widely throughout the body. The highest amounts were located in the bone, kidneys, liver, spleen and testes. Retention of vanadium was reported, particularly in bone (WHO, 2000; NTP, 2002; EFSA, 2004). Limited data indicate that vanadium binds to transferrin in plasma in humans (NTP, 2002).

 

Excretion

Absorbed vanadium is predominantly excreted via urine. In rats and mice, vanadium is eliminated from plasma in three phases (plasma half times of 15 minutes, 14 hours and 8.5 days (EFSA, 2004)). In humans, initial clearance via urine is rapid, followed by a slower phase. About 60% of absorbed vanadium is excreted by the kidneys within 24 hours (NTP, 2002).

 

 

Azay, J., Bres, J., Krosniak, M., Tesseidre, P.-L., Cabanis, J.-C., Serrano, J.-J. and Cros, G.

Vanadium pharmacokinetics and oral bioavailability upon single-dose administration of vanadyl sulfate to rats.

Fundamental Clinical Pharmacology15(5): 313-324,2001

 

Conklin, A.W., C.S. Skinner, T.L. Felten and C.L. Sanders.

Clearance and distribution of intratracheally instilled vanadium-48 compounds in the rat.

Toxicol. Lett. 11(1-2): 199-204, 1982

 

Curran, G.L., D.L. Arzarnoff and R.E. Bohnger.

Effect of cholesterol synthesis inhibition in normocholesteremic young men.

J. Clin. Invest. 38: 1251-1261, 1959

 

EFSA. Opinion of the Scientific Panel on Dietetic Products, Nutrition and Allergies on a request from the Commission related to the tolerable upper intake level of vanadium (Request N° EFSA-Q-2003-018); European Food Safety Authority, Parma, Italy. The EFSA Journal 33: 1-22 (2004)

 

IARC. Cobalt Sulfate, Gallium Arsenide, Indium Phospide and Vanadium Pentoxide. IARC Monographs on the evaluation of carcinogenic risks to humans Vol. 86: Summary of data reported and evaluation. International Agency for Research on Cancer,,, 2006.

 

Janssen PJCM,van, Engelen JGM van, Schielen PCJI, Wouters MFA.

Maximum permissible risk levels for human intake of soil contaminants: fourth series of compounds.

RIVM report No. 711701004; National Institute for Public Health and the Environment, Bilthoven, The Netherlands. 1998

 

NTP. Technical report on the toxicology and carcinogenesis studies of vanadium pentoxide (CAS no. 1314-62-1) in F344/N rats and B6C3F1 mice (inhalation studies).

National Toxicology Program, Technical Report Series No 507, NIH Publication no. 03-4441. Dept. of Health and Human Services,,. 2002

 

NTP test proposal.NTP Board of Scientific Counselors Meeting, June 11-12, 2008

 

Wiegman, T.B., H.D. Day and R.V. Patak.

Intestinal absorption and secretion of radioactive vanadium (⁴⁸VO₃^-) in rats and effect of Al(OH)₃.

J. Toxicol. Environ. Health. 10: 233-245, 1982

 

WHO. Air Quality Guidelines - Second Edition; Chapter 6.12: Vanadium.

World Health Organization, Regional Office for Europe, 2000

 

Discussion on bioaccumulation potential result:

Toxicokinetics

 

Absorption

In general, available data indicate that in both animals and humans, absorption of vanadium via the gastrointestinal tract is low.Vanadium in the vanadate (+5) state is absorbed about three to five times more effectively than in the vanadyl (+4) state (NTP,2008).Based on the poor absorption of vanadium from the GI tract, internal tissue concentrations and toxicity from oral exposure are expected to be low.Ingested vanadium is absorbed poorly by the gastrointestinal tract of humans. Only 0.1-1.0% of a 100 and 125 mg dose of diammonium oxytartarovanadate was absorbed gastrointestinally, and 60% of the absorbed dose was excreted by the kidneys within 24 hours (Curran et al, 1959). An oral dose of 0.3 mg/kg vanadium from vanadium pentoxide administered to rats resulted in only 2.6% being absorbed (Conklin et al, 1982). Wiegman et al studied the absorbtion and excretion of radioactive vanadium in rats. Vanadium was administered as sodium metavanadate by gavage (5μmol, corresponding to 0.255 mg vanadium). After 4 days, 18% of the dose was excreted in urine and 69% was recovered in the faeces. The remainder was retained in various organs and tissues. When A1(OH)₃gel was given to the rats at the same time as vanadium administration, aluminum hydroxide decreased the absorbtion of vanadium, 8% of the administered radioactivity being recovered in the urine and 86% recovered in the faeces.One study reported by Azay et al on the bioavailability of vanadium from vanadium sulphate after oral gavage administration of 7.5 and 15 mg vanadium/kg to rats indicates higher absorption, estimated to be 16.8 and 12.5 %, as determined from area under the curve (AUC) data compared with intravenous administration.

 

Dermal exposure is also reported to result in poor absorption (Janssen et al., 1998; EFSA, 2004; IARC, 2006).

 

Absorption of vanadium in the lungs following inhalation exposure is higher and depends on particle size and the solubility of the vanadium compound (Janssen et al., 1998).Conklin et al. (1982) reported that 100% of an intratracheal dose of 0.3 mg/kg vanadium administered as radiolabeled vanadium pentoxide was absorbed by rats. Approximately 40% of the recovered radioactivity had been cleared from the lungs within 1 hour, and 90% had been cleared within 3 days. Clearance from the lung was primarily into blood, liver and bone, indicating rapid absorption. By post-treatment day 3, 40% of the radioactivity had been recovered in the urine. Similar results were obtained for vanadyl chloride.

 

Distribution

Following oral uptake in rats, vanadium is transported in the serum bound to transferrin and is distributed widely throughout the body. The highest amounts were located in the bone, kidneys, liver, spleen and testes. Retention of vanadium was reported, particularly in bone (WHO, 2000; NTP, 2002; EFSA, 2004). Limited data indicate that vanadium binds to transferrin in plasma in humans (NTP, 2002).

 

Excretion

Absorbed vanadium is predominantly excreted via urine. In rats and mice, vanadium is eliminated from plasma in three phases (plasma half times of 15 minutes, 14 hours and 8.5 days (EFSA, 2004)). In humans, initial clearance via urine is rapid, followed by a slower phase. About 60% of absorbed vanadium is excreted by the kidneys within 24 hours (NTP, 2002).

 

 

Azay, J., Bres, J., Krosniak, M., Tesseidre, P.-L., Cabanis, J.-C., Serrano, J.-J. and Cros, G.

Vanadium pharmacokinetics and oral bioavailability upon single-dose administration of vanadyl sulfate to rats.

Fundamental Clinical Pharmacology15(5): 313-324,2001

 

Conklin, A.W., C.S. Skinner, T.L. Felten and C.L. Sanders.

Clearance and distribution of intratracheally instilled vanadium-48 compounds in the rat.

Toxicol. Lett. 11(1-2): 199-204, 1982

 

Curran, G.L., D.L. Arzarnoff and R.E. Bohnger.

Effect of cholesterol synthesis inhibition in normocholesteremic young men.

J. Clin. Invest. 38: 1251-1261, 1959

 

EFSA. Opinion of the Scientific Panel on Dietetic Products, Nutrition and Allergies on a request from the Commission related to the tolerable upper intake level of vanadium (Request N° EFSA-Q-2003-018); European Food Safety Authority, Parma, Italy. The EFSA Journal 33: 1-22 (2004)

 

IARC. Cobalt Sulfate, Gallium Arsenide, Indium Phospide and Vanadium Pentoxide. IARC Monographs on the evaluation of carcinogenic risks to humans Vol. 86: Summary of data reported and evaluation. International Agency for Research on Cancer,,, 2006.

 

Janssen PJCM,van, Engelen JGM van, Schielen PCJI, Wouters MFA.

Maximum permissible risk levels for human intake of soil contaminants: fourth series of compounds.

RIVM report No. 711701004; National Institute for Public Health and the Environment, Bilthoven, The Netherlands. 1998

 

NTP. Technical report on the toxicology and carcinogenesis studies of vanadium pentoxide (CAS no. 1314-62-1) in F344/N rats and B6C3F1 mice (inhalation studies).

National Toxicology Program, Technical Report Series No 507, NIH Publication no. 03-4441. Dept. of Health and Human Services,. 2002

 

NTP test proposal.NTP Board of Scientific Counselors Meeting, June 11-12, 2008

 

Wiegman, T.B., H.D. Day and R.V. Patak.

Intestinal absorption and secretion of radioactive vanadium (⁴⁸VO₃^-) in rats and effect of Al(OH)₃.

J. Toxicol. Environ. Health. 10: 233-245, 1982

 

WHO. Air Quality Guidelines - Second Edition; Chapter 6.12: Vanadium.

World Health Organization, Regional Office for Europe,,, 2000