Disposition of tungsten in rodents after repeat oral and drinking water exposures

Abstract

Repeat oral doses of tungsten (W) show retention in kidneys, intestine, and femur as well as translocation of small amounts to neonates. Furthermore, W exposure leads to decreased function of molybdenum (Mo)-containing enzymes in kidneys, liver, and intestine. The chemical disposition of W (administered as sodium tungstate dihydrate in water) in plasma, liver, kidneys, uterus, femur, and intestine of rodents (Sprague-Dawley rats and C57Bl/6N mice) was characterized after repeat exposure by gavage (10 mg kg⁻¹) or drinking water (560 mg L⁻¹) for 14 consecutive days. Separately, the same species were exposed to drinking water (560 mg L⁻¹) during gestation for 9 (mice) or 10 (rats) days. For the rodents exposed during gestation, all the aforementioned tissues were analyzed in addition to the fetus to assess transplacental disposition. Animals were euthanized 24 h after the last day of dosing. At sacrifice, plasma, intestine, liver, kidneys, femur, uterus, and fetus were collected for analysis by inductively coupled plasma mass spectrometry. W was detectable in plasma and all tissues and in fetus of both rats and mice. W accumulation occurred in intestine, kidneys, and femur. The possible sources for enrichment/retention in these tissues include the intestine being the primary route of entry for oral exposures, kidneys being the primary route of elimination (>95% excreted through the urine as shown in previous studies), and the ability of W to displace phosphate in bone and be retained in the femur. Enzyme activity of Mo-dependent enzymes xanthine oxidase (XO) and sulfite oxidase (SO) was also evaluated in liver, intestine, and kidneys due to the propensity of W to substitute for Mo. Enzyme activity was reduced in kidneys and intestine, while it was unaltered in liver.

Keywords:

• tungsten
• rodents
• disposition

Acknowledgements

This work was supported by Contract Number N01-ES-25483 from the National Institute of Environmental Health Sciences (NIEHS). We thank Dr L.T. Burka and Dr M.L. Cunningham at NIEHS for their critical review of the manuscript.