Toxicological evaluation of vanadium and derivation of a parenteral tolerable intake value for medical devices
Charlotte E Laupheimer, Yana Kolianchuk, Rex FitzGerald, Martin F. Wilks, Arne Jaksch
Abstract
Vanadium is used in alloys, batteries as well as catalyst and is a known impurity in medical devices and pharmaceuticals. The present work describes the calculation of a parenteral tolerable intake (TI) for vanadium by chronic exposure in implantable medical devices per ISO 10993–17:2023, the applicable standard. The 2023 update of ISO 10993-17 [1] introduces new uncertainty factors (UFs) for calculating a TI. Therefore, we noted differences between the ISO guidance and the ICH Q3D guidance on Permissible Daily Exposure (PDE) for parental elemental pharmaceutical impurities. We derived a TI of 0.20 μg V/kg/day based on the updated ISO guidance, and a PDE of 0.24 μg V/kg/day based on ICH guidance. The latter is considered a more realistic estimate. • Vanadium (V) has been used for many years in titanium aluminium vanadium alloys for medical devices. • This analysis collates the widely diverging opinions of regulatory agencies on vanadium reference values. • The recent 3-month NTP toxicity studies of NaVO 3 and VOSO 4 triggered the re-evaluation of vanadium's TI for medical devices. • The derivation of a parenteral TI for vanadium in compliance with the revised ISO 10993–17:2023.