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Measurement, model prediction and uncertainty quantification of plasma clearance of cerium citrate in humans

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Abstract

Double tracer studies in healthy human volunteers with stable isotopes of cerium citrate were performed with the aim of investigating the gastro-intestinal absorption of cerium (Ce), its plasma clearance and urinary excretion. In the present work, results of the clearance of Ce in blood plasma are shown after simultaneous intravenous and oral administration of a Ce tracer. Inductively coupled plasma mass spectrometry was used to determine the tracer concentrations in plasma. The results show that about 80% of the injected Ce citrate cleared from the plasma within the 5 mins post-administration. The data obtained are compared to a revised biokinetic model of Ce, which was initially developed by the International Commission on Radiological Protection (ICRP). The measured plasma clearance of Ce citrate was mostly consistent with that predicted by the ICRP biokinetic model. Furthermore, in an effort to quantify the uncertainty of the model prediction, the laboratory animal data on which the ICRP biokinetic Ce model is based, was analyzed. The measured plasma clearance and its uncertainty was also compared to the plasma clearance uncertainty predicted by the model. It was found that the measured plasma clearance during the first 15 min after administration is in a good agreement with the modelled plasma clearance. In general, the measured clearance falls inside the 95% confidence interval predicted by the biokinetic model.

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References

  • Aeberhardt A, Nizza P, Remy J, Boilleau Y (1962) Etude comparee du métabolisme du cérium 144 en fonction de son état physico-chimique chez le rat. Int J Radiat Biol 5(3):217–246

    Google Scholar 

  • Barrett PHR, Bell BM, Cobelli C, Golde H, Schumitzky A, Vicini P, Foster DM (1998) SAAM II: simulation, analysis, and modeling software for tracer and pharmacokinetic studies. Metabolism 47:484–492

    Google Scholar 

  • Cantone MC, de Bartolo D, Gambarini G, Giussani A, Molho N, Pirola L, Hansen C, Werner E, Roth P (1993) Intestinal absorption of tellurium studied with stable tracers. J Radioanal Nucl Chem 170(2):433–442

    Google Scholar 

  • Cantone MC, De Bartolo D, Giussani A, Roth P, Werner E (1998) The stable isotope approach to elemental biokinetics. Radiat Phys Chem 51:589

    ADS  Google Scholar 

  • Currie LA (1968) Limits for qualitative detection and quantitative determination. Anal Chem 40:586–593

    Google Scholar 

  • De Grazia JA, Ivanovic P, Fellows H, Rich C (1965) A double-isotope method for measurement of intestinal absorption of calcium in man. J Lab Clin Med 66(5):822–829

    Google Scholar 

  • Durbin PW, Asling GW, Johnston ME, Hamilton JG, Williams MH (1955) The metabolism of the lanthanons in the rat ii. time studies of the tissue deposition of intravenously administered radioisotopes. Report Number: UCRL-3191. Lawrence Radiation Laboratory, Berkeley

    Google Scholar 

  • EPA (2012) Rare earth elements: a review of production, processing, recycling, and associated environmental issues. US Environmental Protection Agency, Washington, DC

    Google Scholar 

  • Giussani A, Cantone MC, Gerstmann U, Greiter M, Hertenberger R, Höllriegl V, Leopold K, Veronese I, Oeh U (2008) Biokinetics of ruthenium isotopes in humans and its dependence on chemical speciation. Paper presented at the 12th International Congress of the International Radiation Protection Association, Buenos Aires, Argentina,

  • Greiter MB, Giussani A, Höllriegl V, Li WB, Oeh U (2011) Human biokinetic data and a new compartmental model of zirconium—a tracer study with enriched stable isotopes. Sci Total Environ 409:3701–3710

    ADS  Google Scholar 

  • Health Effects Institute (2001) Evaluation of human health risk from cerium added to diesel fuel. Health Effects Institute Communication 9, Boston MA

    Google Scholar 

  • Heitland P, Köster H (2006) Biomonitoring of 37 trace elements in blood samples from inhabitants of northern Germany by ICP-MS. J Trace Elem Med Biol 20:253–262

    Google Scholar 

  • Höllriegl V, Li WB, Oeh U (2006) Human biokinetics of strontium. part II: final data evaluation of intestinal absorption and urinary excretion of strontium in human subjects after stable tracer administration. Radiat Environ Biophys 45:179–185

    Google Scholar 

  • Höllriegl V, Gonzalez-Estecha M, Trasobares EM, Giussani A, Oeh U, Herraiz MA, Michalke B (2010) Measurement of cerium in human breast milk and blood samples. J Trace Elem Med Biol 24(3):193–199

    Google Scholar 

  • Höllriegl V, Li WB, Michalke B (2017) Biokinetic measurements and modelling of urinary excretion of cerium citrate in humans. Radiat Environ Biophys 56(1):1–8

    Google Scholar 

  • IAEA (1998) Evaluation the reliability of predictions made using environmental transfer models. International Atomic Energy Agency, Vienna

    Google Scholar 

  • ICRP (1989) Age-dependent doses to members of the public from intake of radionuclides: part 1: ingestion dose coefficients. ICRP Publication 56. Pergamon Press, Oxford

    Google Scholar 

  • ICRP (1993) Age-dependent doses to members of the public from intake of radionuclides: part 2: ingestion dose coefficients. ICRP Publication 67. Pergamon Press, Oxford

    Google Scholar 

  • ICRP (2006) Human alimentary tract model for radiological protection. ICRP Publication 100. Elsevier, Oxford, UK

    Google Scholar 

  • Iman RL, Shortencarier MJ (1984) A FORTRAN 77 program and user’s guide for the generation of Latin hypercube and random samples for use with computer models. NUREGKR-3624 (SAND83-2365) Sandia National Laboratories, Albuquerque

    Google Scholar 

  • ISO (2005) General requirements for the competence of testing and calibration laboratories, vol ISO/IEC 17025:2005. International Organization for Standardization, Geneva

    Google Scholar 

  • ISO, Bipm, IEC, Ifcc, IUPAC, IUPAP, OIML (1995) Guide to the expression of uncertainty in measurement (GUM), 1st edn. International Organization for Standardization, Geneva

    Google Scholar 

  • Jakupec MA, Unfried P, Keppler BK (2005) Pharmacological properties of cerium compounds. Rev Physiol Biochem Pharmacol 153:101–111

    Google Scholar 

  • Keiser T, Höllriegl V, Giussani A, Oeh U (2011) Measuring technique for thermal ionisation mass spectrometry of human tracer kinetic study with stable cerium isotopes. Isotopes Environ Health Stud 47(2):238–252

    Google Scholar 

  • Leggett RW (2001) Reliability of the ICRP’s dose coefficients for members of the public. 1. sources of uncertainty in the biokinetic models. Radiat Prot Dosim 95:199–213

    Google Scholar 

  • Leggett RW, Ansoborlo E, Bailey M, Gregoratto D, Paquet F, Taylor DM (2014) Biokinetic data and models for occupational intake of lanthanoids. Int J Radiat Biol 90:996–1010

    Google Scholar 

  • Li WB, Greiter M, Oeh U, Hoeschen C (2011) Reliability of a new biokinetic model of zirconium in internal dosimetry. part I. parameter uncertainty analysis. Health Phys 101(6):660–676

    Google Scholar 

  • Li XF, Chen ZB, Chen ZQ, Zhang YH (2013) A human health risk assessment of rare earth elements in soil and vegetables from a mining in Fujian province, southeast China. Chemospere 93:1240–1246

    ADS  Google Scholar 

  • Li XF, Chen ZB, Chen ZQ (2014) Distribution and fractionation of rare earth elements in soil-water system and human blood and hair from a mining area in south-west fujian province, china. Environ Earth Sci 72:3599–3608

    Google Scholar 

  • Li WB, Klein W, Blanchardon E, Puncher M, Leggett RW, Oeh U, Breustedt B, Noßke D, Lopez MA (2015) Parameter uncertainty analysis of a biokinetic model of caesium. Radiat Prot Dosim 163(1):37–57

    Google Scholar 

  • Linsalata P, Eisenbud M, Penna Franca F (1986) Ingestion estimates of Th and the light rare earth elements based on measurements on human feces. Health Phys 50(1):163–167

    Google Scholar 

  • Minoia C, Sabbioni E, Apostoli P, Pietra R, Pozzoli L, Gallorini M, Nicolau G, Alessio L, Capodaglio E (1990) Trace element reference values in tissues from inhabitants of the european community. I. a study of 46 elements in urine, blood and serum of italian subjects. Sci Total Environ 95:89–105

    ADS  Google Scholar 

  • Moore FD, Olesen KH, McMurrey JD, Parker HV, Ball NR, Boyden CM (1963) The body cell mass and its supporting environment: body composition in health and in disease. W.B Saunders Company, Philadelphia

    Google Scholar 

  • Morgan M, Henrion M (1990) Uncertainty a guide to dealing with uncertainty in quantitative risk and policy analysis. Cambridge University Press, New York

    Google Scholar 

  • NCRP (1996) A guide for uncertainty analysis in dose and risk assessments related to environmental contamination. National Council on Radiation Protection and Measurements, Bethesda

    Google Scholar 

  • NCRP (1998) Evaluating the reliability of biokinetic and dosimetric models and parameters used to assess individual doses for risk assessment purposes. National Council on Radiation Protection and Measurements, Bethesda

    Google Scholar 

  • NCRP (2009) Uncertainty in internal radiation dose assessment. National Council on Radiation Protection and Measurement, Bethesda

    Google Scholar 

  • Ohyoshi A, Ohyoshi E, Ono H, Yamakawa S (1972) A study of citrate complexes of several lanthanides. J Inorganic Nucl Chem 34:1955–1960

    Google Scholar 

  • Pagano G, Guida M, Tommasi F, Oral R (2015) Health effects and toxicity mechanisms of rare earth elements-knowledge gaps and research prospects. Ecotoxicol Environ Saf 115:40–48

    Google Scholar 

  • Paquet F, Frelont S, Cote G, Madic C (2003) The contribution of chemical speciation to internal dosimetry. Radiat Prot Dosim 105(1–4):179–184

    Google Scholar 

  • Pourmand A, Dauphas N (2010) Distribution coefficients of 60 elements on TODGA resin: application to Ca, Lu, Hf. U Th Isot Geochem Tantala 81(3):741–753

    Google Scholar 

  • Prakash D, Gabani P, Chandel AK, Ronen Z, Singh OV (2013) Bioremediation: a genuine technology to remediate radionuclides from the environment. Microb Biotechnol 6(4):349–360

    Google Scholar 

  • Rosoff B, Siegel E, Williams GL, Spencer H (1963) Distribution and excretion of radioactive rare-earth compounds in mice. Int J Appl Radiat Isot 14:129–135

    Google Scholar 

  • Roth P, Heinrichs U, Giussani A, Zilker T, Felgenhauer N, Greim H (1999) Internal biokinetic behaviour of molybdenum in humans studied with stable isotopes as tracers. Isot Environ Health Stud 33:323–329

    Google Scholar 

  • Sabbioni E, Pietra R, Gaglione P (1982) Long-term occupational risk of rare-earth pneumoconiosis. a case report as investigated by neuron activation analysis. Sci Tot Environ 26:19–32

    Google Scholar 

  • Sappakitkamjorn J, Niwitpong S (2013) Confidence intervals for the coefficients of variation with bounded parameters. Int J Mathe Comput Phys Electr Comput Eng 7(9):1416–1421

    Google Scholar 

  • Spencer H Metabolism and removal of some radioisotopes in man. In: 65 IP (ed) In: Diagnosis and Treatment of Radioactive Poisioning. Proceedings of a scientific meeting held at Vienna (A), 15-18 October 1962, jointly organized by WHO and IAEA., 1963. WHO and IAEA,

  • Stanek EJ, Calabrese EJ, Barnes R, Pekow P (1997) Soil ingestion in adults-results of a second pilot study. Ecotoxicol Environ Saf 36:249–257

    Google Scholar 

  • Taylor DM, Leggett RW (1998) A generic biokinetic model for the lanthanide elements. Radiat Prot Dosim 79:351–354

    Google Scholar 

  • Taylor DM, Leggett RW (2003) A generic biokinetic model for predicting the behaviour of the lanthanide elements in the human body. Radiat Prot Dosim 105:193–198

    Google Scholar 

  • Turner GA, Taylor DM (1968) The transport of plutonium, americium and curium in the blood of rats. Phys Med Biol 13(4):535–546

    Google Scholar 

  • Tyler G (2004) Rare earth elements in soil and plant systems-a review. Plant Soil 267:191–206

    Google Scholar 

  • Veronese I, Giussani A, Cantone MC, de Bartolo D, Roth P, Werner E (2001) Kinetics of systemic ruthenium in human blood using a stable tracer. J Radiol Prot 21:31–38

    Google Scholar 

  • Veronese I, Giussani A, Cantone MC, Birattari C, Bonardi M, Groppi F, Höllriegl V, Roth P, Werner E (2004) Influence of the chemical form on the plasma clearance of ruthenium in humans. Appl Radiat Isot 60:7–13

    Google Scholar 

  • Wappelhorst O, Kuehn I, Heidenreich H, Markert B (2002) Transfer of selected elements from food into human milk. Nutrition 18(4):316–322

    Google Scholar 

  • Zhang ZY, Chai ZF (2004) Isotopic tracer studies of chemical behavior of rare earth elements in environmental and biological sciences. Radiochim Acta 92:355–358

    Google Scholar 

  • Zheltonozhsky V, Mück K, Bondarkov M (2001) Classification of hot particles from the Chernobyl accident and nuclear weapons detonations by non-destructive methods. J Environ Radioact 57:151–166

    Google Scholar 

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Acknowledgements

We gratefully thank Mrs. Sabrina Beutner for the ICPMS measurements. This work was supported by the German Federal Ministry of Education and Research (BMBF) with contract number 02NUK030A. We thank the reviewers and journal editor for valuable comments and linguistic revisions.

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Authors and Affiliations

  1. Institute of Radiation Medicine, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany

    Vera Höllriegl, Vladimir Spielmann & Wei Bo Li

  2. Institute of Resource Ecology, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01328, Dresden, Germany

    Astrid Barkleit

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  1. Vera Höllriegl
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Correspondence to Vera Höllriegl.

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Höllriegl, V., Barkleit, A., Spielmann, V. et al. Measurement, model prediction and uncertainty quantification of plasma clearance of cerium citrate in humans. Radiat Environ Biophys 59, 121–130 (2020). https://doi.org/10.1007/s00411-019-00823-z

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