3-Month toxicity studies of tetravalent and pentavalent vanadium compounds in HSD

Abstract

The National Toxicology Program performed 3-month toxicity studies of tetravalent (vanadyl sulfate; VS) and pentavalent (sodium metavanadate; SM) vanadium compounds in drinking water, due to potential human exposure and lack of robust toxicity data. Time-mated Hsd:Sprague Dawley SD rats were exposed via dosed drinking water during gestation (beginning GD6) and lactation. Pups were exposed in utero, during lactation, and continued exposure for 3 months post-weaning. Adult B6C3F1/N mice were exposed for 3 months. Animals were exposed to VS at 0, 21, 41.9, 83.8, 167.5 or 335 mg/L, or to SM at 0, 31.3, 62.5, 125, 250 or 500 mg/L. There was higher moribundity in the 500 mg/L SM dams and pups throughout the postnatal period. There were lower percent live pups at birth (-25%), lower number of viable pups at PND4 (-45%; pre-standardization) and throughout lactation after litter standardization (-28%; PND4-28) compared to controls. There were no effects on littering or pup survival in VS exposed dams or pups. For both compounds, in rats and mice, water consumption (g/day) was lower in correlation with increasing exposure concentration. At study termination, there were lower body weights observed at the highest concentration for rats (-14 to -20%) and mice (-12 to -27%) exposed to SM and mice exposed to VS (-9 to -12%). In male and female mice exposed to SM, there were consistent increases in erythrocytes and reticulocytes and deceases in hematocrit and hemoglobin; changes in rats and in VS exposed animals were sporadic. In general, organ weight effects were attributed to body weight changes, except for treatment-related decreases in thymus weights for SM mice. Histopathological findings were limited for both sex/species, exposed to either compound. Based on plasma and urine total vanadium levels, and estimated vanadium consumption from water consumption data, the exposure to vanadium from SM appears to be higher than from VS. For both SM and VS, internal exposure increased proportionally with increasing estimated vanadium consumption. In general, effects were more frequently observed in SM exposed animals which may be attributable to higher systemic exposure to vanadium at similar compound concentrations.