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

Greiter, Matthias; Giussani, A.; Höllriegl, Vera; Li, Wei Bo; Oeh, Uwe

doi:10.1016/j.scitotenv.2011.06.031

Cited by 12 publications

(14 citation statements)

References 18 publications

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“…Some of the transfer rates and compartments of the ICRP model are however physiologically questionable: The direct mass transport from the two bone compartments to the urinary bladder contents and upper large intestine compartments or the distinction between trabecular bone surface and cortical bone surface as such. In order to address these shortcomings, we have recently proposed the alternative HMGU model [6] combining the two bone compartments into one single compartment and replacing these mass flows by physiologically more plausible transfer rates (Figure 1B). Altogether both models share eight transfer rates, which we denoted by x 1 ,…, x 8 .…”

Section: Methodsmentioning

confidence: 99%

“…The human biokinetic data was measured in a stable tracer study executed at the Helmholtz Zentrum München (HMGU) [6,25]. It includes 16 investigations of 12 healthy humans with ingestion of a investigation-specific amount of isotopically enriched stable zirconium.…”

Section: Methodsmentioning

confidence: 99%

“…The parameters of this model were mostly derived from animal data. In order to obtain more reliable dose estimates for humans, the Helmholtz Zentrum München (HMGU) developed a new, physiologically more plausible biokinetic model [6]. It is based on the processing of non-radioactive Zr isotopes in 16 investigations with 12 healthy human subjects.…”

Section: Introductionmentioning

confidence: 99%

“…The HMGU and ICRP models were compared based on in vivo plasma and urine data of 16 investigations of 12 human subjects [6] using Bayes factors. More precisely, the models were evaluated for each investigation individually and for the concatenated data of all investigations.…”

Section: Introductionmentioning

confidence: 99%

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Bayesian model selection validates a biokinetic model for zirconium processing in humans

Schmidl

Hug

et al. 2012

BMC Syst Biol

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BackgroundIn radiation protection, biokinetic models for zirconium processing are of crucial importance in dose estimation and further risk analysis for humans exposed to this radioactive substance. They provide limiting values of detrimental effects and build the basis for applications in internal dosimetry, the prediction for radioactive zirconium retention in various organs as well as retrospective dosimetry. Multi-compartmental models are the tool of choice for simulating the processing of zirconium. Although easily interpretable, determining the exact compartment structure and interaction mechanisms is generally daunting. In the context of observing the dynamics of multiple compartments, Bayesian methods provide efficient tools for model inference and selection.ResultsWe are the first to apply a Markov chain Monte Carlo approach to compute Bayes factors for the evaluation of two competing models for zirconium processing in the human body after ingestion. Based on in vivo measurements of human plasma and urine levels we were able to show that a recently published model is superior to the standard model of the International Commission on Radiological Protection. The Bayes factors were estimated by means of the numerically stable thermodynamic integration in combination with a recently developed copula-based Metropolis-Hastings sampler.ConclusionsIn contrast to the standard model the novel model predicts lower accretion of zirconium in bones. This results in lower levels of noxious doses for exposed individuals. Moreover, the Bayesian approach allows for retrospective dose assessment, including credible intervals for the initially ingested zirconium, in a significantly more reliable fashion than previously possible. All methods presented here are readily applicable to many modeling tasks in systems biology.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Bayesian model selection validates a biokinetic model for zirconium processing in humans

Schmidl

Hug

et al. 2012

BMC Syst Biol

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“…The half-life and the removal fraction in each compartment (T 1/2 and ␣ j,i ) can be obtained from analysis of the amount of a radionuclide in different organs and tissues in human autopsies (e.g., bone and soft tissues) if the exposures or the intakes of a radionuclide of a cohort are known, or can be derived from the environmental measurements (e.g., concentration in air, water, and foodstuffs). By other methods, like the double tracer technique (Hö llriegl et al 2006;Li et al 2006;Greiter et al 2011), the model parameters can be evaluated from blood clearance and excreta attained by biokinetic investigations on humans and laboratory animals. The uncertainty of the transfer rate parameters (k j,i ) of the ICRP model were calculated from the uncertainty of removal fractions (␣ j,i ) and rates ( i ) by using Equation (7).…”

Section: Icrp Systemic Biokinetic Modelmentioning

confidence: 99%

Reliability of a New Biokinetic Model of Zirconium in Internal Dosimetry: Part I, Parameter Uncertainty Analysis

Greiter

Oeh

et al. 2011

Health Physics

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The reliability of biokinetic models is essential in internal dose assessments and radiation risk analysis for the public, occupational workers, and patients exposed to radionuclides. In this paper, a method for assessing the reliability of biokinetic models by means of uncertainty and sensitivity analysis was developed. The paper is divided into two parts. In the first part of the study published here, the uncertainty sources of the model parameters for zirconium (Zr), developed by the International Commission on Radiological Protection (ICRP), were identified and analyzed. Furthermore, the uncertainty of the biokinetic experimental measurement performed at the Helmholtz Zentrum München-German Research Center for Environmental Health (HMGU) for developing a new biokinetic model of Zr was analyzed according to the Guide to the Expression of Uncertainty in Measurement, published by the International Organization for Standardization. The confidence interval and distribution of model parameters of the ICRP and HMGU Zr biokinetic models were evaluated. As a result of computer biokinetic modelings, the mean, standard uncertainty, and confidence interval of model prediction calculated based on the model parameter uncertainty were presented and compared to the plasma clearance and urinary excretion measured after intravenous administration. It was shown that for the most important compartment, the plasma, the uncertainty evaluated for the HMGU model was much smaller than that for the ICRP model; that phenomenon was observed for other organs and tissues as well. The uncertainty of the integral of the radioactivity of 95 Zr up to 50 y calculated by the HMGU model after ingestion by adult members of the public was shown to be smaller by a factor of two than that of the ICRP model. It was also shown that the distribution type of the model parameter strongly influences the model prediction, and the correlation of the model input parameters affects the model prediction to a certain extent depending on the strength of the correlation. In the case of model prediction, the qualitative comparison of the model predictions with the measured plasma and urinary data showed the HMGU model to be more reliable than the ICRP model; quantitatively, the uncertainty model prediction by the HMGU systemic biokinetic model is smaller than that of the ICRP model. The uncertainty information on the model parameters analyzed in this study was used in the second part of the paper regarding a sensitivity analysis of the Zr biokinetic models. Health Phys. 101(6):660 -676; 2011

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Magnesium degradation products: Effects on tissue and human metabolism

Seitz

Eifler

Bach

et al. 2013

J Biomedical Materials Res

112

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Owing to their mechanical properties, metallic materials present a promising solution in the field of resorbable implants. The magnesium metabolism in humans differs depending on its introduction. The natural, oral administration of magnesium via, for example, food, essentially leads to an intracellular enrichment of Mg(2+) . In contrast, introducing magnesium-rich substances or implants into the tissue results in a different decomposition behavior. Here, exposing magnesium to artificial body electrolytes resulted in the formation of the following products: magnesium hydroxide, magnesium oxide, and magnesium chloride, as well as calcium and magnesium apatites. Moreover, it can be assumed that Mg(2+) , OH(-) ions, and gaseous hydrogen are also present and result from the reaction for magnesium in an aqueous environment. With the aid of physiological metabolic processes, the organism succeeds in either excreting the above mentioned products or integrating them into the natural metabolic process. Only a burst release of these products is to be considered a problem. A multitude of general tissue effects and responses from the Mg's degradation products is considered within this review, which is not targeting specific implant classes. Furthermore, common alloying elements of magnesium and their hazardous potential in vivo are taken into account.

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

Cited by 12 publications

References 18 publications

Bayesian model selection validates a biokinetic model for zirconium processing in humans

Bayesian model selection validates a biokinetic model for zirconium processing in humans

Reliability of a New Biokinetic Model of Zirconium in Internal Dosimetry: Part I, Parameter Uncertainty Analysis

Magnesium degradation products: Effects on tissue and human metabolism

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