The Experts below are selected from a list of 10065 Experts worldwide ranked by ideXlab platform

Seokhwan Hwang - One of the best experts on this subject based on the ideXlab platform.

  • Effects of temperature and pH on the biokinetic properties of thiocyanate biodegradation under autotrophic conditions
    Water research, 2012
    Co-Authors: Jaai Kim, Kyungjin Cho, Gyuseong Han, Changsoo Lee, Seokhwan Hwang
    Abstract:

    The simultaneous effects of temperature and pH on the biokinetic properties of thiocyanate biodegradation under mixed-culture, autotrophic conditions were investigated using response surface analysis (RSA) combined with biokinetic modeling. A partial cubic model, based on substrate inhibition Biokinetics, was constructed for each kinetic coefficient in Andrew model (i.e., maximum specific growth rate (μm), saturation coefficient (KS), and substrate inhibition coefficient (KSI)). Each model proved statistically reliable to approximate the responses of the kinetic coefficients to temperature and pH changes (r2 > 0.8, p < 0.05). The response surface plots demonstrated that the biokinetic coefficients change with respect to temperature and pH significantly and in different ways. The model response surfaces were substantially different to each other, indicating distinct correlations between the independent (temperature and pH) and dependent (model response) variables in the models. Based on the estimated response surface models, temperature was shown to have significant effects on all biokinetic coefficients tested. A dominant influence of temperature on μm response was observed while the interdependence of temperature and pH was apparent in the KS and KSI models. Specific growth rate (μ) versus substrate (i.e., thiocyanate) concentration plots simulating using the obtained response surface models confirmed the significant effects of temperature and pH on the microbial growth rate and therefore on the thiocyanate degradation rate. Overall, the response surface models able to describe the biokinetic effects of temperature and pH on thiocyanate biodegradation within the explored region (20–30 °C and pH 6.0–9.0) were successfully constructed and validated, providing fundamental information for better process control in thiocyanate treatment.

  • Biokinetics in acidogenesis of highly suspended organic wastewater by adenosine 5 triphosphate analysis
    Biotechnology and Bioengineering, 2002
    Co-Authors: Conly L. Hansen, Seokhwan Hwang
    Abstract:

    In this paper, we pointed out the problems of using conventional volatile suspended solids (VSS) and chemical oxygen demand (COD) to evaluate biokinetic coefficients, especially for the treatment of highly suspended organic wastewater. We also introduced a novel approach to evaluate biokinetic coefficients by measurement of adenosine 5'-triphosphate (ATP) of microorganisms. The concept of using ATP analysis in biokinetic evaluations with highly suspended wastewater was shown to be effective. This study also showed that the conventional VSS and COD methods were strongly affected by incoming suspended organics in the wastewater and by Biokinetics of microorganisms. A cheese-processing wastewater was used in evaluating the Biokinetics of mesophilic acidogens. The concentration of COD and total suspended solids in the wastewater was 63.3 g/L and 12.4 g/L, respectively. The TSS was 23.6% of total solids concentration. A high ratio of VSS to total suspended solids of 96.7% indicated that most of the suspended particles were organic materials. Lactose and protein were the major organic components contributing COD in the wastewater, and a total of 94.2% of the COD in the wastewater was due to the presence of lactose and protein. Two different physiological conditions where the maximum rates of acetate and butyrate production occurred were tested. These were pH 7 (condition A for acetate production) and pH 7.3 (condition B for butyrate production) at 36.2C, respectively. Based on the molecular structures of the major organic substances and microbial ATP analysis, the residual substrate and microbial concentrations were stoichiometrically converted to substrate COD (SuCOD) and microbial VSS (MVSS), respectively, using correlation coefficients reported previously. These SuCOD and MVSS were simultaneously used to evaluate the biokinetic coefficients using Monod-based mathematical equations. The nonlinear least squares method with 95% confidence interval was used to evaluate biokinetic coefficients. The maximum microbial growth rate, mu(max) and half saturation coefficient, K(s), for conditions A and B were determined to be 9.9 +/- 0.3 and 9.3 +/- 1.0 day(-1) and 134.0 +/- 58.3 and 482.5 +/- 156.5 mg SuCOD/L, respectively. The microbial yield coefficient, Y, and microbial decay rate coefficient, k(d) for conditions A and B were determined to be 0.29 +/- 0.03 and 0.20 +/- 0.05 mg MVSS/mg SuCOD, and 0.14 +/- 0.05 and 0.25 +/- 0.05 day(-1), respectively. Specific substrate utilization rate at condition B was 43.8 +/- 20.6 mg SuCOD/mg MVSS/day, which was 31% higher than that at condition A.

  • Biokinetics in acidogenesis of highly suspended organic wastewater by adenosine 5′ triphosphate analysis
    Biotechnology and bioengineering, 2002
    Co-Authors: Conly L. Hansen, Seokhwan Hwang
    Abstract:

    In this paper, we pointed out the problems of using conventional volatile suspended solids (VSS) and chemical oxygen demand (COD) to evaluate biokinetic coefficients, especially for the treatment of highly suspended organic wastewater. We also introduced a novel approach to evaluate biokinetic coefficients by measurement of adenosine 5'-triphosphate (ATP) of microorganisms. The concept of using ATP analysis in biokinetic evaluations with highly suspended wastewater was shown to be effective. This study also showed that the conventional VSS and COD methods were strongly affected by incoming suspended organics in the wastewater and by Biokinetics of microorganisms. A cheese-processing wastewater was used in evaluating the Biokinetics of mesophilic acidogens. The concentration of COD and total suspended solids in the wastewater was 63.3 g/L and 12.4 g/L, respectively. The TSS was 23.6% of total solids concentration. A high ratio of VSS to total suspended solids of 96.7% indicated that most of the suspended particles were organic materials. Lactose and protein were the major organic components contributing COD in the wastewater, and a total of 94.2% of the COD in the wastewater was due to the presence of lactose and protein. Two different physiological conditions where the maximum rates of acetate and butyrate production occurred were tested. These were pH 7 (condition A for acetate production) and pH 7.3 (condition B for butyrate production) at 36.2C, respectively. Based on the molecular structures of the major organic substances and microbial ATP analysis, the residual substrate and microbial concentrations were stoichiometrically converted to substrate COD (SuCOD) and microbial VSS (MVSS), respectively, using correlation coefficients reported previously. These SuCOD and MVSS were simultaneously used to evaluate the biokinetic coefficients using Monod-based mathematical equations. The nonlinear least squares method with 95% confidence interval was used to evaluate biokinetic coefficients. The maximum microbial growth rate, mu(max) and half saturation coefficient, K(s), for conditions A and B were determined to be 9.9 +/- 0.3 and 9.3 +/- 1.0 day(-1) and 134.0 +/- 58.3 and 482.5 +/- 156.5 mg SuCOD/L, respectively. The microbial yield coefficient, Y, and microbial decay rate coefficient, k(d) for conditions A and B were determined to be 0.29 +/- 0.03 and 0.20 +/- 0.05 mg MVSS/mg SuCOD, and 0.14 +/- 0.05 and 0.25 +/- 0.05 day(-1), respectively. Specific substrate utilization rate at condition B was 43.8 +/- 20.6 mg SuCOD/mg MVSS/day, which was 31% higher than that at condition A.

Wen-xiong Wang - One of the best experts on this subject based on the ideXlab platform.

  • Biokinetics and subcellular distribution of metals in daphnia magna following zn exposure implication for metal regulation
    Science of The Total Environment, 2019
    Co-Authors: Chunmei Zhao, Wen-xiong Wang
    Abstract:

    Abstract Although many studies have addressed the effects of various physicochemical and biological factors on metal bioaccumulation in aquatic organisms, the influences of metal exposure history have drawn much less attention. In the present study, we investigated the effects of different Zn exposure regimes (concentration: 1–200 μg/L, duration: 1–7 d) on the subsequent Biokinetics, metallothionien-like protein (MTLP) induction and subcellular distribution of Cd and Zn in Daphnia magna. Zn body burden increased significantly with elevated exposure concentrations, but was kept within a narrow range regardless of the 200-fold variation of Zn concentrations. Significant induction (7–14 folds) of MTLP by Zn exposure was evident, but was decoupled from the Zn body accumulation. Under different regimes of Zn exposure, Zn was evenly distributed in insoluble (cellular debris, intracellular organelles and metal-rich granules) and soluble fractions (heat sensitive protein and MTLP). However, >60% of Cd was bound with MTLP regardless of the exposure concentration and duration. The biokinetic processes including uptake from the dissolved phase, food assimilation and excretion of Cd and Zn were quantified with radioactive tracers. The uptake rate constants of Cd and Zn from the dissolved phase either remained comparable or increased following Zn pre-exposure, and the efflux of Zn increased by nearly two-fold to counteract the increased uptake from water. The dietary assimilation of Zn also decreased significantly in response to Zn exposure. However, Cd assimilation efficiency was kept relatively constant in each Zn pre-exposure regime. Our results showed that Zn exposure had significant influences on the Biokinetics and physiology of daphnids. Daphnids attempted to maintain the Zn body burden within a narrow range by modification of biokinetic processes instead of subcellular distribution.

  • Aging Influences on the Biokinetics of Functional TiO2 Nanoparticles with Different Surface Chemistries in Daphnia magna.
    Environmental science & technology, 2018
    Co-Authors: Wenhong Fan, Wen-xiong Wang
    Abstract:

    Nanoparticles functionalized with various surface capping moieties are now widely used in different fields, thus there is a major need to understand the behavior and fate of these nanoparticles in the environment. The present study investigated the Biokinetics of fresh titanium dioxide nanoparticles (TiO2 NPs) or TiO2 NPs aged under artificial sunlight (16 h light: 8 h dark) for 1, 3, and 5 days, respectively. Two commercial functionalized TiO2 NPs (with SiO2 coating or SiO2 and polydimethylsiloxane coating) were employed in this study. Dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), and contact angle (CA) measurements demonstrated that the surface properties had changed due to the degradation during aging. The biokinetic parameters including dissolved uptake and depuration rate constant as well as bioconcentration factors were calculated by a biokinetic model. All the biokinetic parameters were significantly dependent on the aging process. Further data analysis showed tha...

  • Aging Influences on the Biokinetics of Functional TiO2 Nanoparticles with Different Surface Chemistries in Daphnia magna
    2018
    Co-Authors: Wenhong Fan, Wen-xiong Wang
    Abstract:

    Nanoparticles functionalized with various surface capping moieties are now widely used in different fields, thus there is a major need to understand the behavior and fate of these nanoparticles in the environment. The present study investigated the Biokinetics of fresh titanium dioxide nanoparticles (TiO2 NPs) or TiO2 NPs aged under artificial sunlight (16 h light: 8 h dark) for 1, 3, and 5 days, respectively. Two commercial functionalized TiO2 NPs (with SiO2 coating or SiO2 and polydimethylsiloxane coating) were employed in this study. Dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), and contact angle (CA) measurements demonstrated that the surface properties had changed due to the degradation during aging. The biokinetic parameters including dissolved uptake and depuration rate constant as well as bioconcentration factors were calculated by a biokinetic model. All the biokinetic parameters were significantly dependent on the aging process. Further data analysis showed that the CA of the TiO2 NPs affected the uptake rate constant and the fast compartmental efflux, and both CA and hydrodynamic diameter affected the fast compartmental efflux. These results were due to the changes of corresponding indexes during the aging process. Our work highlighted the necessity of monitoring the physicochemical indexes of functionalized NPs during aging in evaluation of their environmental risks

  • Why mercury concentration increases with fish size? Biokinetic explanation.
    Environmental pollution (Barking Essex : 1987), 2012
    Co-Authors: Fei Dang, Wen-xiong Wang
    Abstract:

    In field-collected juvenile blackhead seabream Acanthopagrus schlegeli schlegeli, measured total mercury (THg) and methylmercury (MeHg) concentrations were related to 0.19 and 0.33 power of fish mass over a wide size range (more than 50-fold). The causative factors remain unclear. In this study, size-dependent biokinetic parameters for both inorganic mercury [Hg(II)] and MeHg were estimated, and their relative contributions to size-related Hg accumulation were further assessed. Except for the MeHg dietary assimilation efficiency (AE), which was not affected by the fish size, other examined biokinetic parameters showed either positive (Hg(II) AE) or negative correlations (growth rate constant-g, dissolved uptake rate constant-k(u) and efflux rate constant-k(e)) with fish size. The biokinetic variation explained the observed allometric pattern of Hg accumulation in juveniles. Especially, both size-related g and k(e) were the key drivers. The current study addressed the importance of size-related Biokinetics, in particular the k(e) and g, which have important implications to manage Hg contamination in fisheries.

  • comparative approaches to understand metal bioaccumulation in aquatic animals
    Comparative Biochemistry and Physiology C-toxicology & Pharmacology, 2008
    Co-Authors: Wen-xiong Wang, P S Rainbow
    Abstract:

    Over the past decades, comparative physiology and biochemistry approaches have played a significant role in understanding the complexity of metal bioaccumulation in aquatic animals. Such a comparative approach is now further aided by the biokinetic modeling approach which can be used to predict the rates and routes of metal bioaccumulation and assist in the interpretation of accumulated body metal concentrations in aquatic animals. In this review, we illustrate a few examples of using the combined comparative and biokinetic modeling approaches to further our understanding of metal accumulation in aquatic animals. We highlight recent studies on the different accumulation patterns of metals in different species of invertebrates and fish, and between various aquatic systems (freshwater and marine). Comparative metal Biokinetics can explain the differences in metal bioaccumulation among bivalves, although it is still difficult to explain the evolutionary basis for the different accumulated metal body concentrations (e.g., why some species have high metal concentrations). Both physiological/biochemical responses and metal geochemistry are responsible for the differences in metal concentrations observed in different populations of aquatic species, or between freshwater and marine species. A comparative approach is especially important for metal biology research, due to the very complicated and potentially variable physiological handling of metals during their accumulation, sequestration, distribution and elimination in different aquatic species or between different aquatic systems.

R W Leggett - One of the best experts on this subject based on the ideXlab platform.

  • Updated biokinetic model for systemic americium.
    Journal of radiological protection : official journal of the Society for Radiological Protection, 2019
    Co-Authors: R W Leggett, Eric Blanchardon
    Abstract:

    The biokinetic model for systemic americium (Am) currently recommended by the International Commission on Radiological Protection (ICRP) for application to occupational intake of Am is based on information available through the early 1990s. Much additional information on Am Biokinetics has been developed in the past 25 y, including measurements of retention and excretion of 241Am in many workers with 241Am burdens and post mortem measurements of 241Am in tissues of some of those workers. The ICRP's current Am model is reasonably consistent with the updated information, with the main exception that the current model apparently overestimates 24-hour urinary Am as a fraction of skeletal or systemic Am at late times after intake. This paper provides an overview of current information on the systemic kinetics of Am in adult human subjects and laboratory animals and presents an updated biokinetic model for systemic Am that addresses the discrepancies between the current database and current ICRP systemic model for Am. This model is applied in Part 4 (to appear) of an ICRP series of reports on intake of radionuclides by workers called the OIR (Occupational Intake of Radionuclides) series.

  • A generic biokinetic model for noble gases with application to radon.
    Journal of radiological protection : official journal of the Society for Radiological Protection, 2013
    Co-Authors: R W Leggett, J. W. Marsh, Demetrio Gregoratto, Eric Blanchardon
    Abstract:

    To facilitate the estimation of radiation doses from intake of radionuclides, the International Commission on Radiological Protection (ICRP) publishes dose coefficients (dose per unit intake) based on reference biokinetic and dosimetric models. The ICRP generally has not provided biokinetic models or dose coefficients for intake of noble gases, but plans to provide such information for (222)Rn and other important radioisotopes of noble gases in a forthcoming series of reports on occupational intake of radionuclides (OIR). This paper proposes a generic biokinetic model framework for noble gases and develops parameter values for radon. The framework is tailored to applications in radiation protection and is consistent with a physiologically based biokinetic modelling scheme adopted for the OIR series. Parameter values for a noble gas are based largely on a blood flow model and physical laws governing transfer of a non-reactive and soluble gas between materials. Model predictions for radon are shown to be consistent with results of controlled studies of its Biokinetics in human subjects.

  • The Biokinetics of ruthenium in the human body
    Radiation protection dosimetry, 2011
    Co-Authors: R W Leggett
    Abstract:

    The Biokinetics of ruthenium (Ru) in the human body is of interest due mainly to the potential for occupational or environmental exposure to 106Ru (T1/2 = 373.6 d) and 103Ru (T1/2 = 39.3 d), which typically represent a significant portion of the fission products in a reactor inventory. During reactor operations or nuclear fuel reprocessing these ruthenium isotopes may be present as ruthenium tetroxide (RuO4) vapor, a highly mobile form of ruthenium that has been involved in a number of cases of accidental exposure to 106Ru or 103Ru. This paper summarizes the biokinetic database for ruthenium and proposes a new respiratory model for inhaled RuO4 vapor, a new biokinetic for systemic (absorbed) ruthenium, and material-specific gastrointestinal absorption fractions for ruthenium. The proposed respiratory model for RuO4 differs from the current ICRP model mainly in that it depicts slower clearance of deposited activity from the respiratory tract and lower absorption to blood than depicted in the current ICRP model. The proposed systemic biokinetic model depicts more realistic paths of movement of absorbed ruthenium in the body than the current ICRP model and, in contrast to the present model, a less uniform distribution of systemic activity. Implications of the proposed models withmore » regard to inhalation and ingestion dose coefficients for 106Ru are examined.« less

  • A generic biokinetic model for predicting the behaviour of the lanthanide elements in the human body.
    Radiation protection dosimetry, 2003
    Co-Authors: David Taylor, R W Leggett
    Abstract:

    Information on the Biokinetics of the 15 elements of the lanthanide series, 57 La to 71 Lu, is too sparse to permit individual development of meaningful biokinetic models to describe the behaviour of each of the elements in humans. The lanthanides show a regular gradation in chemical properties across the series, and animal studies indicate that this is reflected in regular differences in their deposition in tissues such as the liver and skeleton. These regular differences in chemical and biological behaviour have been utilised to construct a generic lanthanide biokinetic model and to define element-specific parameters for each element in the series. This report describes the use of the available biokinetic data for humans and animals to derive the parameters for each of the elements.

  • The Biokinetics of uranium migrating from embedded DU fragments
    Journal of Environmental Radioactivity, 2002
    Co-Authors: R W Leggett, T.c Pellmar
    Abstract:

    Military uses of depleted uranium (DU) munitions have resulted in casualties with embedded DU fragments. Assessment of radiological or chemical health risks from these fragments requires a model relating urinary U to the rate of migration of U from the fragments, and its accumulation in systemic tissues. A detailed biokinetic model for U has been published by the International Commission on Radiological Protection (ICRP), but its applicability to U migrating from embedded DU fragments is uncertain. Recently, Pellmar and colleagues (1999) conducted a study at the Armed Forces Radiobiology Research Institute (AFRRI) on the redistribution and toxicology of U in rats with implanted DU pellets, simulating embedded fragments. This paper compares the biokinetic data from that study with the behavior of commonly studied forms of U in rats (e.g., intravenously injected U nitrate). The comparisons indicate that the Biokinetics of U migrating from embedded DU is similar to that of commonly studied forms of U with regard to long-term accumulation in kidneys, bone, and liver. The results provide limited support for the application of the ICRP's model to persons with embedded DU fragments. Additional information is needed with regard to the short-term behavior of migrating U and its accumulation in lymph nodes, brain, testicles, and other infrequently studied U repositories.

E Blanchardon - One of the best experts on this subject based on the ideXlab platform.

  • Updated biokinetic model for systemic americium
    Journal of Radiological Protection, 2019
    Co-Authors: R. Leggett, E Blanchardon
    Abstract:

    The biokinetic model for systemic americium (Am) currently recommended by the International Commission on Radiological Protection (ICRP) for application to occupational intake of Am is based on information available through the early 1990s. Much additional information on Am Biokinetics has been developed in the past 25 y, including measurements of retention and excretion of 241Am in many workers with 241Am burdens and post mortem measurements of 241Am in tissues of some of those workers. The ICRP's current Am model is reasonably consistent with the updated information, with the main exception that the current model apparently overestimates 24-hour urinary Am as a fraction of skeletal or systemic Am at late times after intake. This paper provides an overview of current information on the systemic kinetics of Am in adult human subjects and laboratory animals and presents an updated biokinetic model for systemic Am that addresses the discrepancies between the current database and current ICRP systemic model for Am. This model is applied in Part 4 (to appear) of an ICRP series of reports on intake of radionuclides by workers called the OIR (Occupational Intake of Radionuclides) series. © 2019 Not subject to copyright in the USA. Contribution of Oak Ridge National Laboratory.

  • Eurados coordinated action on research, quality assurance and training of internal dose assessments
    RADIATION PROTECTION DOSIMETRY, 2011
    Co-Authors: M A Lopez, Bastian Breustedt, Augusto Giussani, E Blanchardon, D. Broggio, D. Franck, I. Balásházy, P. Berard, C.m. Castellani, C. Hurtgen
    Abstract:

    EURADOS working group on 'Internal Dosimetry (WG7)' represents a frame to develop activities in the field of internal exposures as coordinated actions on quality assurance (QA), research and training. The main tasks to carry out are the update of the IDEAS Guidelines as a reference document for the internal dosimetry community, the implementation and QA of new ICRP biokinetic models, the assessment of uncertainties related to internal dosimetry models and their application, the development of physiology-based models for Biokinetics of radionuclides, stable isotope studies, biokinetic modelling of diethylene triamine pentaacetic acid decorporation therapy and Monte-Carlo applications to in vivo assessment of intakes. The working group is entirely supported by EURADOS; links are established with institutions such as IAEA, US Transuranium and Uranium Registries (USA) and CEA (France) for joint collaboration actions. © The Author 2010. Published by Oxford University Press. All rights reserved.

  • THE CONRAD APPROACH TO BIOKINETIC MODELING OF DTPA DECORPORATION THERAPY
    Health Physics, 2010
    Co-Authors: Bastian Breustedt, Augusto Giussani, Paul Fritsch, Jean Piechowski, Philippe Bérard, E Blanchardon, M A Lopez, Andrea Luciani, Dietmar Nosske, Jutta Schimmelpfeng
    Abstract:

    Diethylene Triamine Pentaacetic Acid (DTPA) is used for decorporation of plutonium because it is known to be able to enhance its urinary excretion for several days after treatment by forming stable Pu-DTPA complexes. The decorporation prevents accumulation in organs and results in a dosimetric benefit, which is difficult to quantify from bioassay data using existing models. The development of a biokinetic model describing the mechanisms of actinide decorporation by administration of DTPA was initiated as a task in the European COordinated Network on RAdiation Dosimetry (CONRAD). The systemic biokinetic model from Leggett et al. and the biokinetic model for DTPA compounds of International Commission on Radiological Protection Publication 53 were the starting points. A new model for Biokinetics of administered DTPA based on physiological interpretation of 14 C-labeled DTPA studies from literature was proposed by the group. Plutonium and DTPA Biokinetics were modeled separately. The systems were connected by means of a second order kinetics process describing the chelation process of plutonium atoms and DTPA molecules to Pu-DTPA complexes. It was assumed that chelation only occurs in the blood and in systemic compartment ST0 (representing rapid turnover soft tissues), and that Pu-DTPA complexes and administered forms of DTPA share the same biokinetic behavior. First applications of the CONRAD approach showed that the enhancement of plutonium urinary excretion after administration of DTPA was strongly influenced by the chelation rate constant. Setting it to a high value resulted in a good fit to the observed data. However, the model was not yet satisfactory since the effects of repeated DTPA administration in a short time period cannot be predicted in a realistic way. In order to introduce more physiological knowledge into the model several questions still have to be answered. Further detailed studies of human contamination cases and experimental data will be needed in order to address these issues. The work is now continued within the European Radiation Dosimetry Group, EURADOS.

  • The CONRAD approach to biokinetic modeling of DTPA decorporation therapy
    Health Physics, 2010
    Co-Authors: A.-l. Sérandour, Bastian Breustedt, Augusto Giussani, Paul Fritsch, Philippe Bérard, E Blanchardon, M A Lopez, Dietmar Nosske, A Luciani, Jean Piechowski
    Abstract:

    Diethylene Triamine Pentaacetic Acid (DTPA) is used for decorporation of plutonium because it is known to be able to enhance its urinary excretion for several days after treatment by forming stable Pu-DTPA complexes. The decorporation prevents accumulation in organs and results in a dosimetric benefit, which is difficult to quantify from bioassay data using existing models. The development of a biokinetic model describing the mechanisms of actinide decorporation by administration of DTPA was initiated as a task in the European COordinated Network on RAdiation Dosimetry (CONRAD). The systemic biokinetic model from Leggett et al. and the biokinetic model for DTPA compounds of International Commission on Radiological Protection Publication 53 were the starting points. A new model for Biokinetics of administered DTPA based on physiological interpretation of C-labeled DTPA studies from literature was proposed by the group. Plutonium and DTPA Biokinetics were modeled separately. The systems were connected by means of a second order kinetics process describing the chelation process of plutonium atoms and DTPA molecules to Pu-DTPA complexes. It was assumed that chelation only occurs in the blood and in systemic compartment ST0 (representing rapid turnover soft tissues), and that Pu-DTPA complexes and administered forms of DTPA share the same biokinetic behavior. First applications of the CONRAD approach showed that the enhancement of plutonium urinary excretion after administration of DTPA was strongly influenced by the chelation rate constant. Setting it to a high value resulted in a good fit to the observed data. However, the model was not yet satisfactory since the effects of repeated DTPA administration in a short time period cannot be predicted in a realistic way. In order to introduce more physiological knowledge into the model several questions still have to be answered. Further detailed studies of human contamination cases and experimental data will be needed in order to address these issues. The work is now continued within the European Radiation Dosimetry Group, EURADOS. Copyright © 2010 Health Physics Society.

  • Study of the influence of radionuclide Biokinetics on the efficiency of in vivo counting using Monte Carlo simulation
    Health Physics, 2009
    Co-Authors: S. Lamart, E Blanchardon, A. Molokanov, G.h. Kramer, D. Broggio, D. Franck
    Abstract:

    To improve calibration methods of in vivo counting, our laboratory has developed a computer tool to model internal contamination and assess in vivo activity and corresponding organ absorbed doses. The aim of the recent work was to define a more realistic source based on biokinetic models. The influence of the biokinetic parameters on the in vivo counting was studied through the simulation of an acute inhalation intake of Am. The tissue distribution of activity predicted by the biokinetic model was visualized. Two equivalent methods for determination of the efficiency related to the total activity distributed in the body were used. The comparison between the efficiency taking the Biokinetics into account and the classically estimated efficiency quantifies the influence of the activity distribution in the body and provides conversion factors for correcting the classical efficiency to account for Biokinetics. ©2009Health Physics Society.

Bas J. Blaauboer - One of the best experts on this subject based on the ideXlab platform.

  • new approach methodologies nams for human relevant Biokinetics predictions meeting the paradigm shift in toxicology towards an animal free chemical risk assessment
    ALTEX-Alternatives to Animal Experimentation, 2020
    Co-Authors: Ans Punt, Bas J. Blaauboer, Hans Bouwmeester, Sandra Coecke, Betty C Hakkert, Delilah F G Hendriks, Paul Jennings, Nynke I Kramer, Sibylle Neuhoff, Rosalinde Masereeuw
    Abstract:

    For almost fifteen years, the availability and regulatory acceptance of new approach methodologies (NAMs) to assess the absorption, distribution, metabolism and excretion (ADME/Biokinetics) in chemical risk evaluations are a bottleneck. To enhance the field, a team of 24 experts from science, industry, and regulatory bodies, including new generation toxicologists, met at the Lorentz Centre in Leiden, The Netherlands. A range of possibilities for the use of NAMs for Biokinetics in risk evaluations were formulated (for example to define species differences and human variation or to perform quantitative in vitro-in vivo extrapolations). To increase the regulatory use and acceptance of NAMs for Biokinetics for these ADME considerations within risk evaluations, the development of test guidelines (protocols) and of overarching guidance documents is considered a critical step. To this end, a need for an expert group on Biokinetics within the Organisation of Economic Cooperation and Development (OECD) to supervise this process was formulated. The workshop discussions revealed that method development is still required, particularly to adequately capture transporter mediated processes as well as to obtain cell models that reflect the physiology and kinetic characteristics of relevant organs. Developments in the fields of stem cells, organoids and organ-on-a-chip models provide promising tools to meet these research needs in the future.

  • CHAPTER 11:Big Data and Biokinetics
    Issues in Toxicology, 2019
    Co-Authors: Miyoung Yoon, Gina Song, Harvey J. Clewell, Bas J. Blaauboer
    Abstract:

    The new paradigm for toxicity testing and safety assessment replaces the emphasis from being based on apical endpoints in animal studies to an approach incorporating knowledge of modes of action in human cellular systems together with Biokinetics. With this shift, there is an increasing demand for rapid evaluation and prediction of Biokinetics. The development of an easy-to-use and robust computational approach based on alternative approaches is critically required to fully incorporate Biokinetics into modern toxicity testing, particularly to accommodate the need to translate a large amount of information from high-throughput in vitro toxicity assays results. This chapter describes the use of big data to define a comprehensive physiological/biochemical modelling framework to rapidly predict in vivo Biokinetics of chemicals. The ultimate goal is to support interpretation of high-volume toxicity data on large numbers of chemicals in an efficient way while increasing in vivo relevance in the context of human safety.

  • The in vitro Biokinetics of chlorpromazine and diazepam in aggregating rat brain cell cultures after repeated exposure.
    Toxicology in vitro : an international journal published in association with BIBRA, 2014
    Co-Authors: Jessica J W Broeders, Bas J. Blaauboer, Joop L M Hermens, Mariegabrielle Zurich
    Abstract:

    Neurotoxic effects of compounds can be tested in vitro using cell systems. One example is aggregating rat brain cell cultures. For the extrapolation of in vitro data to the in vivo situation, it is important to take the Biokinetics of the test compound into account. In addition, the exposure in vivo is often for a longer period of time; therefore, it is crucial to incorporate this into in vitro assays as well. In this study, aggregating rat brain cell cultures were exposed to chlorpromazine (CPZ) and diazepam (DZP) for 12-days with repeated exposure. Samples were taken from the stocks, test media, cell culture media and cells at specific time points on the first and last exposure day. These samples were analysed by HPLC-UV. The amount of CPZ in the medium decreased over time, whereas the amount in the cells showed an increase. Accumulation of CPZ in the cells was seen over the 12-day repeated exposure. The amount of DZP in the medium remained stable over time and only up to 2% of DZP added was found in the cells. Different biokinetic behaviour was found for CPZ and DZP. Possible explanations are differences in uptake into the cells or efflux out of the cells. The decrease of CPZ in the medium versus the stable amount of DZP results in differences in exposure concentrations over time, which should be taken into account when interpreting in vitro effect data.

  • Biokinetic modeling and in vitro-in vivo extrapolations.
    Journal of toxicology and environmental health. Part B Critical reviews, 2010
    Co-Authors: Bas J. Blaauboer
    Abstract:

    The introduction of in vitro methodologies in the toxicological risk assessment process requires a number of prerequisites regarding both the toxicodynamics and the Biokinetics of the compounds under study. In vitro systems will need to be relevant for measuring those structural and physiological changes that are good indicators for adverse effects. Furthermore, the dose metric found to have an effect in the in vitro system should be relevant. One element in defining the appropriate dose metric is related to the kinetic behavior of the compound in the in vitro system: binding to proteins, binding to plastic, evaporation, and the interaction between the culture medium and the cells. Ways to measure and model "in vitro Biokinetics" are described. Second, the appropriate dose metric in vitro, e.g., the effective concentration, will need to be extrapolated to relevant in vivo exposure scenarios. The application of physiologically based biokinetic modelling is essential in such extrapolations. The parameters needed to build these models often can be estimated based on nonanimal data, namely chemical properties (QSARs) and in vitro experiments.

  • Biokinetic and toxicodynamic modelling and its role in toxicological research and risk assessment.
    Alternatives to laboratory animals : ATLA, 2003
    Co-Authors: Bas J. Blaauboer
    Abstract:

    Toxicological risk assessment for chemicals is still mainly based on highly standardised protocols for animal experimentation and exposure assessment. However, developments in our knowledge of general physiology, in chemicobiological interactions and in (computer-supported) modelling, have resulted in a tremendous change in our understanding of the molecular mechanisms underlying the toxicity of chemicals. This permits the development of biologically based models, in which the Biokinetics as well as the toxicodynamics of compounds can be described. In this paper, the possibilities are discussed of developing systems in which the systemic (acute and chronic) toxicities of chemicals can be quantified without the heavy reliance on animal experiments. By integrating data derived from different sources, predictions of toxicity can be made. Key elements in this integrated approach are the evaluation of chemical functionalities representing structural alerts for toxic actions, the construction of biokinetic models on the basis of non-animal data (for example, tissue-blood partition coefficients, in vitro biotransformation parameters), tests or batteries of tests for determining basal cytotoxicity, and more-specific tests for evaluating tissue or organ toxicity. It is concluded that this approach is a useful tool for various steps in toxicological hazard and risk assessment, especially for those forms of toxicity for which validated in vitro and other non-animal tests have already been developed.