Systemic exposure and urinary excretion of vanadium following perinatal subchronic exposure to vanadyl sulfate and sodium metavanadate via drinking water

Abstract

Vanadium is a ubiquitous environmental contaminant although there are limited data to assess potential adverse human health impact following oral exposure. In support of studies investigating the subchronic toxicity of vanadyl sulfate (V⁴⁺) and sodium metavanadate (V⁵⁺) following perinatal exposure via drinking water in male and female rats, we have determined the internal exposure and urinary excretion of total vanadium at the end of study. Water consumption decreased with increasing exposure concentration following exposure to both compounds. Plasma and urine vanadium concentration normalized to total vanadium consumed per day increased with the exposure concentration of vanadyl sulfate and sodium metavanadate suggesting absorption increased as the exposure concentration increased. Additionally, females had higher concentrations than males (in plasma only for vanadyl sulfate exposure). Animals exposed to sodium metavanadate had up to 3-fold higher vanadium concentration in plasma and urine compared to vanadyl sulfate exposed animals, when normalized to total vanadium consumed per day, demonstrating differential absorption, distribution, metabolism, and excretion properties between V⁵⁺ and V⁴⁺ compounds. These data will aid in the interpretation of animal toxicity data of V⁴⁺ and V⁵⁺ compounds and determine the relevance of animal toxicity findings to human exposures.

Keywords: Plasma vanadium; Sodium metavanadate; Urine vanadium; Vanadate; Vanadyl; Vanadyl sulfate.

Figure 1.

Structures of A) vanadyl sulfate and B) sodium metavanadate

Figure 2.

Mean concentration (± SE) of vanadium in A) plasma and B) urine following perinatal exposure of male and female rats to vanadyl sulfate (V⁴⁺) via drinking water. Data are shown for N=3-5 animals per exposure group per sex. Individual data values are shown with points, and values below the limit of detection (LOD) are marked with “x.” Statistical comparisons were not performed when 80% or more of the control values were below the LOD. Statistical significance for an exposure group indicates a significant pairwise test compared to the control group (** p<0.01). Statistical significance for a control group indicates a significant trend test (** p<0.01). Because values in control male group were below LOD, a statistical significance could not be established for males.

Figure 3.

Plasma vanadium concentration normalized to vanadium consumed following perinatal exposure of male and female rats to vanadyl sulfate (V⁴⁺) and sodium metavanadate (V⁵⁺) via drinking water. Exposure groups 1, 2, 3, 4, and 5 (vanadyl sulfate only), respectively, for vanadyl sulfate are 21, 41.9, 83.8, 168, and 335 mg/L and for sodium metavanadate are 31.3, 62.5, 125, 250, and 500 mg/L. Plasma for 500 mg/L sodium metavanadate were not available for analysis.

Figure 4.

Urine vanadium concentration normalized to vanadium consumed following perinatal exposure of male and female rats to vanadyl sulfate (V⁴⁺) and sodium metavanadate (V⁵⁺) via drinking water. Exposure groups 1, 2, 3, 4, and 5 (vanadyl sulfate only), respectively, for vanadyl sulfate are 21, 41.9, 83.8, 168, and 335 mg/L and for sodium metavanadate are 31.3, 62.5, 125, 250, and 500 mg/L. Urine for 500 mg/L sodium metavanadate was not available for analysis.

Figure 5.

Mean concentration (± SE) of vanadium in A) plasma and B) urine following perinatal exposure of male and female rats to sodium metavanadate (V⁵⁺) via drinking water. Data shown are for N=3-5 animals per exposure group per sex. Individual data values are shown with points, and values below the limit of detection (LOD) are marked with “x.” Statistical comparisons were not performed when 80% or more of the control values were below the LOD. Because values in control groups were below LOD, a statistical significance between control and exposed groups could not be established.

Figure 5.

Mean concentration (± SE) of vanadium in A) plasma and B) urine following perinatal exposure of male and female rats to sodium metavanadate (V⁵⁺) via drinking water. Data shown are for N=3-5 animals per exposure group per sex. Individual data values are shown with points, and values below the limit of detection (LOD) are marked with “x.” Statistical comparisons were not performed when 80% or more of the control values were below the LOD. Because values in control groups were below LOD, a statistical significance between control and exposed groups could not be established.