Publication related to RSI or an RSI staff member
Derivation of whole blood biomonitoring equivalents for titanium for the interpretation of biomonitoring data.
Authors
- Ramoju, S, Ramoju S, Risk Sciences International, Ottawa, ON, Canada. Electronic address: SRamoju@Risksciences.com.
- Andersen, M E, Andersen ME, Risk Sciences International, Ottawa, ON, Canada.
- Nong, A, Nong A, Health Canada, Ottawa, ON, Canada.
- Karyakina, N, Karyakina N, Risk Sciences International, Ottawa, ON, Canada; University of Ottawa, Ottawa, ON, Canada.
- Shilnikova, N, Shilnikova N, Risk Sciences International, Ottawa, ON, Canada; University of Ottawa, Ottawa, ON, Canada.
- Krishnan, K, Krishnan K, Risk Sciences International, Ottawa, ON, Canada.
- Krewski, D, Krewski D, Risk Sciences International, Ottawa, ON, Canada; University of Ottawa, Ottawa, ON, Canada.
Biomonitoring equivalents (BEs) have been increasingly applied for biomonitoring purposes by regulatory bodies worldwide. The present report describes the development of a BE for titanium based on a 4-step process: (i) identification of a critical study/point of departure (PoD) supporting an established oral exposure guidance value (OEGV);, (ii) review the available oral PK data and application of a pharmacokinetic model for titanium; (iii) selection of the most appropriate biomarker of exposure in a specific tissue and calculation of steady-state tissue levels corresponding to the PoD in the critical study; and (iv) derivation of BE value adjusting for the uncertainties considered in the original OEGV assessment. Using the above 4-step approach, a blood BE value of 32.5 mug titanium/L was derived. Key components of the analysis included a pharmacokinetic model developed by investigators at the Netherlands National Institute of Public Health (RIVM) and a two-year rodent bioassay of titanium conducted by the US National Cancer Institute. The most sensitive pharmacokinetic parameter involved in the current BE derivation is the oral absorption factor of 0.02%. The provisional BE proposed in this article may be updated as new information on the pharmacokinetics of titanium becomes available.
