Human biokinetic data and a new compartmental model of zirconium — A tracer study with enriched stable isotopes

Biokinetic models describing the uptake, distribution and excretion of trace elements are an essential tool in nutrition, toxicology, or internal dosimetry of radionuclides. Zirconium, especially its radioisotope 95Zr, is relevant to radiation protection due to its production in uranium fission and neutron activation of nuclear fuel cladding material. We present a comprehensive set of human data from a tracer study with stable isotopes of zirconium. The data are used to refine a biokinetic model of zirconium.Six female and seven male healthy adult volunteers participated in the study. It includes 16 complete double tracer investigations with oral ingestion and intravenous injection, and seven supplemental investigations. Tracer concentrations were measured in blood plasma and urine collected up to 100 d after tracer administration. The four data sets (two chemical tracer forms in plasma and urine) each encompass 105–240 measured concentration values above detection limits.Total fractional absorption of ingested zirconium was found to be 0.001 for zirconium in citrate-buffered drinking solution and 0.007 for zirconium oxalate solution.Biokinetic models were developed based on the linear first-order kinetic compartmental model approach used by the International Commission on Radiological Protection (ICRP). The main differences of the optimized systemic model of zirconium to the current ICRP model are (1) recycling into the transfer compartment made necessary by the observed tracer clearance from plasma, (2) different parameters related to fractional absorption for each form of the ingested tracer, and (3) a physiologically based excretion pathway to urine.The study considerably expands the knowledge on the biokinetics of zirconium, which was until now dominated by data from animal studies. The proposed systemic model improves the existing ICRP model, yet is based on the same principles and fits well into the ICRP radiation protection approach.

Research highlights
► Data from adult human volunteer study with zirconium with 100 d follow-up period.
► Double tracer study with ingested and injected enriched stable isotopes.
► Evaluation of fractional absorption for two chemical forms of zirconium.
► Biokinetic compartmental model with recycling describes zirconium metabolism.