Forty-eight-year follow-up of a female worker exposed to highly enriched uranium via chronic and acute inhalation.

The United States Transuranium and Uranium Registries (USTUR) is a unique resource of data and materials for studying biokinetics of uranium in the human body. In this study, bioassay data and post-mortem organ activities from a female whole-body USTUR donor who was exposed to highly enriched uranium were analyzed using the IMBA Professional Plus® software to derive the best estimate of the total intake. The resulting radiation doses delivered to this individual's whole body and major target organs were calculated from estimated intake based on case-specific dose coefficients derived using the AIDE® software. Both intake and dose calculations were carried out using the biokinetic and dosimetric models recommended by the International Commission on Radiological Protection (ICRP) in its Occupational Intakes of Radionuclides publication series. Different exposure scenarios including chronic and acute inhalation intakes were tested. A combination of a chronic inhalation intake and two acute inhalation intakes appears to best describe the bioassay data. To fit this female individual's autopsy data, the transfer rate from the liver to the blood was increased by a factor of 8 and the transfer rate from the kidneys to the blood was decreased by a factor of 2.2. This resulted in the best fit to all data (p = 0.519). The total intake was estimated to be 44.1 kBq, and the committed effective dose was 211 mSv with 96.8% contributed by 234U. 96.6% of the committed effective dose was contributed by the lungs. The remaining 3.4% of the committed effective dose was contributed by all systemic tissues and organs with the highest contribution (0.40%) from the red bone marrow. It is concluded that the current ICRP models, with the adjustment for smoking status, adequately describe uranium biokinetics for this individual except retention in the liver and kidneys. However, this study was based on a single case and may not be sufficient to identify any apparent sex-specific differences in uranium biokinetics.

Human exposure to uranium through drinking water and its detrimental impact on the human body organs.

Human exposure to high concentrations of uranium is a major concern due to the risk of developing numerous internal organ malignancies over time. In addition to the numerous attributes of uranium in the nuclear power industry, the radiological characteristics and chemical toxicity of uranium present a substantial risk to human health. This study aims to evaluate potential negative health impacts associated with the ingestion of uranium through drinking water in the Noida and Greater Noida region within the Gautam Buddha districts of Uttar Pradesh (India), due to extreme industrial revolution in this geological location. The mean concentration of uranium in drinking water of the examined area was estimated to range from 0.23 to 78.21 µg l-1. The hair compartment biokinetic model is used to estimate the retention and radiological doses of uranium in distinct organs and tissues. Studies on time-dependent factors revealed variations in uranium retention, with lower levels observed in the Gastrointestinal Tract (GIT) region and higher levels on cortical bone surfaces causes the skeletal deformities. The kidney, liver, and other soft tissues (OST) exhibited a non-saturation pattern in the retention of uranium via exposure of drinking water. The age-wise non-carcinogenic and carcinogenic doses were estimated for the health hazards studies. The outcome of this study will be useful for water resource management authorities to supply safe potable water to the local residents.

Absorbed dose coefficients for pediatric differentiated thyroid cancer patients undergoing radioiodine therapy.

The escalating incidence of differentiated thyroid cancer (DTC) in pediatric patients and the resultant growing use of radioactive iodine (RAI) reinforce the need to evaluate radiation exposure to normal tissues and radiation-induced health risks in pediatric patients undergoing RAI therapy. In the current study, we calculated absorbed dose coefficients (i.e. absorbed dose per unit activity administered, mGy MBq-1) specific for pediatric patients with localized DTC undergoing RAI therapy following total thyroidectomy for use in epidemiological studies. We first modified previously-published biokinetic models for adult thyroid cancer patients to achieve a reasonable agreement with iodine biokinetics observed in pediatric patients or design principles addressed in the International Commission on Radiological Protection (ICRP) reference age-specific biokinetic models. We then combined the biokinetic models in conjunction withSvalues derived from ICRP reference pediatric voxel phantoms. The absorbed dose coefficients for pediatric patients were overall greater than those for adults with a ratio (pediatric/adult) up to 11.6 and rapidly decreased with increasing age. The sensitivity analysis showed that the renal clearance rate andSvalues may have the greatest impact on the absorbed dose coefficients with the rank correlation coefficients ranging from -0.53 to -0.82 (negative correlations) and from 0.51 to 0.80 (positive correlations), respectively. The results of the current study may be utilized in clinical or epidemiological studies to estimate organ-specific radiation absorbed doses and radiation-associated health risks among pediatric thyroid cancer patients.

Machine learning-enhanced stochastic uncertainty and sensitivity analysis of the ICRP human respiratory tract model for an inhaled radionuclide.

The International Commission on Radiological Protection (ICRP) has developed the reference Human Respiratory Tract Model (HRTM), detailed in ICRP Publications 66 and 130, to estimate the deposition and clearance of inhaled radionuclides. These models utilize reference anatomical and physiological parameters for particle deposition (PD). Biokinetic models further estimate retention and excretion of internalized particulates, aiding the derivation of inhalation dose coefficients (DC). This study aimed to assess variability in deterministic131I biokinetic and dosimetry models through stochastic analysis using the updated HRTM from ICRP Publication 130. The complexities of the ICRP PD model were reconstructed into a new, independent computational model. Comparison with reference data for total PD fractions for reference worker, solely a nose breather, covering activity median aerodynamic diameters from 0.3µm to 20µm, showed a 1.04% relative and 0.7% absolute difference, demonstrating good agreement with ICRP deposition fractions. The deterministic DC module was reconstructed in Python and expanded for stochastic analysis, systematically expanding deposition components from HRTM and assigning probability distribution functions to uncertain parameters. These were integrated into an in-house stochastic radiological exposure dose calculator, utilizing latin hypercube sampling. A case of an occupational radionuclide intake was explored, in which biodistribution and committed effective DC (CEDC) were computed for131I type F, considering a lognormal particle size distribution with a median of 5µm. Results showed the published ICRP reference CEDC marginally exceeds the 75th percentile of observed samples, with log-gamma distribution as the best-fit probability distribution. A Random Forest regression model with SHapley Additive exPlanations was employed for sensitivity analysis to predict feature importance. The analysis identified the HRTM particle transport rates scaling factor, followed by the aerodynamic deposition efficiency in the alveolar interstitial region as the most impactful parameters. This study offers a unique stochastic approach on inhaled particulate metabolism, enhancing radiation consequence management, medical countermeasures, and dose reconstruction for epidemiological studies.

Mathematical complexities in radionuclide metabolic modelling: a review of ordinary differential equation kinetics solvers in biokinetic modelling.

Biokinetic models have been employed in internal dosimetry (ID) to model the human body's time-dependent retention and excretion of radionuclides. Consequently, biokinetic models have become instrumental in modelling the body burden from biological processes from internalized radionuclides for prospective and retrospective dose assessment. Solutions to biokinetic equations have been modelled as a system of coupled ordinary differential equations (ODEs) representing the time-dependent distribution of materials deposited within the body. In parallel, several mathematical algorithms were developed for solving general kinetic problems, upon which biokinetic solution tools were constructed. This paper provides a comprehensive review of mathematical solving methods adopted by some known internal dose computer codes for modelling the distribution and dosimetry for internal emitters, highlighting the mathematical frameworks, capabilities, and limitations. Further discussion details the mathematical underpinnings of biokinetic solutions in a unique approach paralleling advancements in ID. The capabilities of available mathematical solvers in computational systems were also emphasized. A survey of ODE forms, methods, and solvers was conducted to highlight capabilities for advancing the utilization of modern toolkits in ID. This review is the first of its kind in framing the development of biokinetic solving methods as the juxtaposition of mathematical solving schemes and computational capabilities, highlighting the evolution in biokinetic solving for radiation dose assessment.

Modelling DTPA therapy following Am contamination in rats.

A major challenge in modelling the decorporation of actinides (An), such as americium (Am), with DTPA (diethylenetriaminepentaacetic acid) is the fact that standard biokinetic models become inadequate for assessing radionuclide intake and estimating the resulting dose, as DTPA perturbs the regular biokinetics of the radionuclide. At present, most attempts existing in the literature are empirical and developed mainly for the interpretation of one or a limited number of specific incorporation cases. Recently, several approaches have been presented with the aim of developing a generic model, one of which reported the unperturbed biokinetics of plutonium (Pu), the chelation process and the behaviour of the chelated compound An-DTPA with a single model structure. The aim of the approach described in this present work is the development of a generic model that is able to describe the biokinetics of Am, DTPA and the chelate Am-DTPA simultaneously. Since accidental intakes in humans present many unknowns and large uncertainties, data from controlled studies in animals were used. In these studies, different amounts of DTPA were administered at different times after contamination with known quantities of Am. To account for the enhancement of faecal excretion and reduction in liver retention, DTPA is assumed to chelate Am not only in extracellular fluids, but also in hepatocytes. A good agreement was found between the predictions of the proposed model and the experimental results for urinary and faecal excretion and accumulation and retention in the liver. However, the decorporation from the skeletal compartment could not be reproduced satisfactorily under these simple assumptions.

Evaluation and updates to the Leggett model for pharmacokinetic modeling of exposure to lead in the workplace - Part II adjustments to the adult exposure model, confirmation of Leggett+, and modeling of workplace exposure.

California's Office of Environmental Health Hazard Assessment has updated the comprehensive age-specific model of lead metabolism in humans published by Richard W. Leggett in 1993. The updated model, called Leggett+, was introduced in a peer-reviewed report in 2013. The Leggett + model simulates the relationship between blood lead and exposure in the workplace. Leggett + includes a workplace exposure model comprising respiratory tract intake (workplace lead inhaled by a worker) and uptake (lead absorbed into the blood from the respiratory tract plus uptake from ambient air and diet). The latter is calculated as intake times an inhalation transfer coefficient plus background uptake. An adjusted adult systemic model describes the metabolism of the absorbed lead. This paper provides details about the workplace exposure and uptake elements of Leggett+, an updated approach to calibrating an inhalation transfer coefficient, confirmation of the model's performance in predicting blood lead levels from workplace studies, and predictions of blood lead levels from simulated exposures to workplace airborne lead over a working lifetime. Blood lead relative to airborne lead concentrations in a standard workplace scenario predicted by Leggett + was similar to corresponding relationships from four published workplace studies. Leggett + predictions displayed a good fit to regression equations when other key factors were considered such as pre-employment blood lead and ongoing background intake of lead, workplace air concentration, lead aerosol characteristics, and worker activity levels. The comprehensive Leggett + model can simulate plausible workplace air-blood lead relationships from a broad range of worker exposures. The inhalation transfer coefficient of 0.30, derived from empirical data described in the 2013 report has been reexamined. The original estimate continues to represent a plausible mid-point for a coefficient derived from an expanded range of theoretical particle size distributions deposited in the upper and lower regions of the respiratory tract considering intake during sedentary and outdoor activity breathing scenarios. This coefficient is slightly lower than the value of 0.35 estimated for unknown forms of lead by Leggett in 1993.

An age- and sex-specific biokinetic model for radon.

Publication 137 of the International Commission on Radiological Protection (ICRP) describes a biokinetic model for radon used to derive dose coefficients for occupational intake of radon isotopes. The model depicts transfer of inhaled or ingested radon to blood, exchange of radon between blood and tissues, and gradual loss of radon from the body based on physical laws governing transfer of a non-reactive and soluble gas between materials. This paper describes an age- and sex-specific variation of that model developed for use in an upcoming ICRP series of reports on environmental intake of radionuclides by members of the public titled 'Dose Coefficients for Intakes of Radionuclides by Members of the Public'. The proposed model modifies the model structure and transfer coefficients presented in Publication 137 to allow more realistic dosimetric treatment of bone marrow and breast and expands the model to address pre-adult ages, based on the physical principles used in the development of the model of Publication 137 together with anatomical and physiological changes occurring during human development.

Mathematical solutions in internal dose assessment: A comparison of Python-based differential equation solvers in biokinetic modeling.

In biokinetic modeling systems employed for radiation protection, biological retention and excretion have been modeled as a series of discretized compartments representing the organs and tissues of the human body. Fractional retention and excretion in these organ and tissue systems have been mathematically governed by a series of coupled first-order ordinary differential equations (ODEs). The coupled ODE systems comprising the biokinetic models are usually stiff due to the severe difference between rapid and slow transfers between compartments. In this study, the capabilities of solving a complex coupled system of ODEs for biokinetic modeling were evaluated by comparing different Python programming language solvers and solving methods with the motivation of establishing a framework that enables multi-level analysis. The stability of the solvers was analyzed to select the best performers for solving the biokinetic problems. A Python-based linear algebraic method was also explored to examine how the numerical methods deviated from an analytical or semi-analytical method. Results demonstrated that customized implicit methods resulted in an enhanced stable solution for the inhaled60Co (Type M) and131I (Type F) exposure scenarios for the inhalation pathway of the International Commission on Radiological Protection (ICRP) Publication 130 Human Respiratory Tract Model (HRTM). The customized implementation of the Python-based implicit solvers resulted in approximately consistent solutions with the Python-based matrix exponential method (expm). The differences generally observed between the implicit solvers andexpmare attributable to numerical precision and the order of numerical approximation of the numerical solvers. This study provides the first analysis of a list of Python ODE solvers and methods by comparing their usage for solving biokinetic models using the ICRP Publication 130 HRTM and provides a framework for the selection of the most appropriate ODE solvers and methods in Python language to implement for modeling the distribution of internal radioactivity.

A 10-step framework for use of read-across (RAX) in next generation risk assessment (NGRA) for cosmetics safety assessment.

This paper presents a 10-step read-across (RAX) framework for use in cases where a threshold of toxicological concern (TTC) approach to cosmetics safety assessment is not possible. RAX builds on established approaches that have existed for more than two decades using chemical properties and in silico toxicology predictions, by further substantiating hypotheses on toxicological similarity of substances, and integrating new approach methodologies (NAM) in the biological and kinetic domains. NAM include new types of data on biological observations from, for example, in vitro assays, toxicogenomics, metabolomics, receptor binding screens and uses physiologically-based kinetic (PBK) modelling to inform about systemic exposure. NAM data can help to substantiate a mode/mechanism of action (MoA), and if similar chemicals can be shown to work by a similar MoA, a next generation risk assessment (NGRA) may be performed with acceptable confidence for a data-poor target substance with no or inadequate safety data, based on RAX approaches using data-rich analogue(s), and taking account of potency or kinetic/dynamic differences.

Bio-electrical stimulation process on degradation of Phenanthrene from aqueous solution using a novel anode modified with carbon cloth: Operational performance, microbial activity and energy.

Phenanthrene as the hazardous PAHs-component are extensively detected in industrial wastewater. However, the impacts of bioelectrostimulation process on Phenanthrene degradation in aerobic reactors remained unclear. Here, a novel bioelectrostimulation process equipped with carbon cloth as electrodes was developed to investigate the removal efficiency of Phenanthrene and ATPase enzyme activity in the synthetic wastewater. The results obtained from the present study indicated that a complete Phenanthrene degradation (100%) can be achieved using microbial electrostimulation systems steel mesh coated with carbon cloth (MES-CC) as anode under optimal operational conditions (electrical current: 4 mA, HA concentration: 15 mg L-1) within 18 h. The conductive carbon cloth provides a biofilm carrier to easily transfer the electrons between electrodes and microbial communities. In addition, the highest ATPase enzyme activity (5176 U) was observed when the aerobic MES-CC reactors were operated with electrical current 4 mA. Furthermore, the COD removal efficiency in MES-CC increased from 49% to 96% when the C: N ratio decreased from 20 to 5. The highest value of Vmax in MES-CC for suspended and attached growth were determined to be 2.87 and 0.54 g COD g-1 biomass. Overall, the results demonstrated that MES equipped with carbon cloth and continuous electrical current mode has good potential for efficient Phenanthrene wastewater treatment.

Assessment and clinical management of internal contamination.

Internal contamination by radionuclides may occur through inhalation, ingestion and absorption through the skin or subcutaneous tissue. The clinical management of internalized radionuclides requires the integration of clinical signs and symptoms with dose estimates in biological tissues obtained from the face, nose, sputum, urine, faeces and/or skin. The assessment of ingested radionuclides includes bioassays of urine and faeces, and if available, whole body counting for radionuclides that emit penetrating x-rays or gamma-rays. An estimate of intake dose may be made at the time of initial patient evaluation by measuring radioactivity, converting counts/minute to depositions/minute with a specific gamma-ray constant, and comparing the amount to its annual limit on intake, clinical decision guide or derived reference level. Since nobody dies from internal contamination per se, medically unstable patients should be stabilized before addressing internal contamination. Whenever possible, internal contaminants should be physically removed as soon as possible after exposure. For inhaled internal contaminants, radionuclide-specific therapy may include the administration of an ion exchange resin (i.e. Prussian blue, PB) or chelating agent (i.e. diethylenetriamine pentaacetate, DTPA, that binds toradioactiveplutonium, americium, and curium), or the physical removal of insoluble particles with a high activity radionuclide (192Ir,90Sr,210Po) by bronchioalveolar lavage. Decorporation with PB, DTPA and other agents is used to enhance excretion. The treatment of wounds contaminated with an actinide includes gentle irrigation, surgical excision of contaminated tissue and DTPA. The averted dose (i.e. the total effective dose averted by therapy) may be calculated for each exposure route.

Investigation of the biological treatability of pistachio processing industry wastewaters in a batch-operated aerobic bioreactor.

This study encompasses investigation of treatment of pistachio processing industry wastewaters in a batch reactor under aerobic conditions, calculation of kinetic parameters and comparison of different inhibition models. The mixed microorganism culture used in the study was adapted to pistachio processing industry wastewaters for nearly one month and then concentrations from 50 to 1000 mg L-1 of pistachio processing industry wastewaters were added to the medium and treatment was investigated in batch experiments. The Andrews, Han-Levenspiel, Luong and Aiba biokinetic equations were chosen for the correlations between the concentration of pistachio processing industry wastewaters and specific growth rates, and the kinetic parameters in these biokinetic equations were calculated. The maximum specific growh rate, semi-saturated constant and inhibition constant parameters, included in the Aiba biokinetic equation providing best fit among the other equations, had values calculated as 0.25 h-1, 19 mg L-1, and 516 mg L-1, respectively. The substrate value reaches maximum value and the specific growth rate at this concentration were calculated as 101.379 mg L-1 and 0.1827 h-1, respectively.

Temperature and oxygen level determine N2 O respiration activities of heterotrophic N2 O-reducing bacteria: Biokinetic study.

Nitrous oxide (N2 O), a potent greenhouse gas, is reduced to N2 gas by N2 O-reducing bacteria (N2 ORB), a process which represents an N2 O sink in natural and engineered ecosystems. The N2 O sink activity by N2 ORB depends on temperature and O2 exposure, yet the specifics are not yet understood. This study explores the effects of temperature and oxygen exposure on biokinetics of pure culture N2 ORB. Four N2 ORB, representing either clade I type nosZ (Pseudomonas stutzeri JCM5965 and Paracoccus denitrificans NBRC102528) or clade II type nosZ (Azospira sp. strains I09 and I13), were individually tested. The higher activation energy for N2 O by Azospira sp. strain I13 (114.0 ± 22.6 kJ mol-1 ) compared with the other tested N2 ORB (38.3-60.1 kJ mol-1 ) indicates that N2 ORB can adapt to different temperatures. The O2 inhibition constants (KI ) of Azospira sp. strain I09 and Ps. stutzeri JCM5965 increased from 0.06 ± 0.05 and 0.05 ± 0.02 µmol L-1 to 0.92 ± 0.24 and 0.84 ± 0.31 µmol L-1 , respectively, as the temperature increased from 15°C to 35°C, while that of Azospira sp. strain I13 was temperature-independent (p = 0.106). Within the range of temperatures examined, Azospira sp. strain I13 had a faster recovery after O2 exposure compared with Azospira sp. strain I09 and Ps. stutzeri JCM5965 (p < 0.05). These results suggest that temperature and O2 exposure result in the growth of ecophysiologically distinct N2 ORB as N2 O sinks. This knowledge can help develop a suitable N2 O mitigation strategy according to the physiologies of the predominant N2 ORB.

A biokinetic model for systemic sodium.

This paper describes an updated biokinetic model for systemic sodium (Na), developed for use in a series of reports by the International Commission on Radiological Protection (ICRP) on occupational intake of radionuclides. In contrast to the ICRP's previous model for intake of radio-sodium by workers, the updated model depicts realistic directions of movement of Na in the body including recycling of activity between blood and tissues. The updated model structure facilitates extension of the baseline transfer coefficients for adults to different age groups and to special exposure scenarios such as transfer of radio-sodium from the mother to the foetus or the nursing infant. Dose coefficients for22Na and24Na based on the updated model generally do not differ greatly from those based on the ICRP's previous Na model when both models are connected to the ICRP's latest dosimetry system. The main exception is that the updated model yields roughly twofold higher dose coefficients for endosteal bone surface than does the previous model due to the dosimetrically cautious assumption in the updated model that exchangeable Na in bone resides on bone surface.

Adjustment of the iodine ICRP population pharmacokinetic model for the use in thyroid cancer patients after thyroidectomy.

Biokinetic models developed for healthy humans are not appropriate to describe biokinetics in thyroid cancer patients following thyroidectomy. The aim of this study was to adjust the population model for iodine proposed by the International Commission on Radiological Protection (ICRP) for the use in these patients. Rate constants of the ICRP publication 128 model for iodine were adjusted using the population modelling software package Monolix to describe activity retention in whole-body, thyroid, blood and protein-bound iodine observed in 23 patients. The new set of rate constants was compared to the four uptake scenarios proposed in ICRP publication 128. Flow from the inorganic iodide in blood compartment into the first thyroid compartment decreases to 0.15 d-1compared to a value of 7.27 d-1for the ICRP publication 128 model with a medium uptake. The transfer from first to second thyroid compartments and the outflow from the second thyroid compartment increases. An increased turnover rate of extrathyroidal organic iodine is observed. The rate constant from inorganic iodide in blood to kidney was also adjusted. Overall a good agreement was found between the adjusted model and the activity retention in thyroid cancer patients. The adjustment of population pharmacokinetic models to describe the biokinetic properties of specific patient populations for therapeutic radiopharmaceuticals is essential to capture the changes in biokinetics. The proposed set of rate constants for the established ICRP publication 128 model can be used to more accurately assess radiation protection requirements for the treatment of thyroid cancer patients using radioiodine.

Korean-specific biokinetic model for iodine in radiological protection.

The International Commission on Radiological Protection (ICRP) recently adopted a detailed biokinetic model for systemic iodine with reference transfer coefficients based on typical worldwide dietary intakes of stable iodine. The regional data provided demonstrate that the ICRP reference thyroidal biokinetics may differ substantially across regions with atypically low or high dietary intakes of stable iodine. Importantly, the design of the ICRP model facilitates modifications of reference thyroidal kinetics based on regional dietary iodine intake. The present study extended the ICRP model to the South Korean population, whose dietary iodine intake is much higher than the global mean. The following three transfer coefficients were selected as targets for Korean-specific values: thyroidal uptake rate (λ1), hormonal secretion rate (λ4) and leakage rate of thyroidal organic iodine as inorganic iodide (λ5). The Korean-specific values forλ1,λ4andλ5were determined to be 4.48, 0.0086 and 0.0171 d-1, respectively, to yield the measurements of thyroidal iodine and physiological status of Korean adults. The determinedλ1andλ5values differed noticeably from the ICRP values, whereas theλ4value was comparable to that of the ICRP. Compared with the ICRP reference model, the Korean model, in which the Korean-specific transfer coefficients were adopted, predicted noticeably lower thyroidal uptake and faster decrease of thyroidal iodine. In addition, the predicted cumulative activities of radioiodine in the thyroid were substantially lower (40-80%) than those predicted by the ICRP model. The Korean model developed in this study demonstrates that the iodine biokinetics for Koreans (i.e. a population with a high iodine consumption) obviously differ from the prediction of the ICRP model. Hence, the Korean model may serve to improve the accuracy of thyroid dose estimation for Koreans and will lead to practical changes in matters concerned with radiological protection.

Biokinetic aspects for biocatalytic remediation of xenobiotics polluted seawater.

AIMS: This research was conducted to investigate the biocatalytic remediation of xenobiotics polluted seawater using two biocatalysts; whole bacterial cells of facultative aerobic halotolerant Corynebacterium variabilis Sh42 and its extracted crude enzymes. METHODS AND RESULTS: One-Factor-at-A-Time technique and statistical analysis were applied to study the effect of initial substrate concentrations, pH, temperature, and initial biocatalyst concentrations on the batch biocatalytic degradation of three xenobiotic pollutants (2-hydroxybiphenyl (2-HBP), catechol and benzoic acid) in artificial seawater (salinity 3·1%). HPLC and gas-chromatography mass spectroscopy analyses were utilized to illustrate the quantitative removal of the studied aromatic xenobiotic pollutants and their catabolic pathway. The results revealed that the microbial and enzymatic cultures followed substrate inhibition kinetics. Yano and Koga's equation showed the best fit for the biokinetic degradation rates of 2-HBP and benzoic acid, whereas Haldane biokinetic model adequately expressed the specific biodegradation rate of catechol. The biokinetic results indicated the good efficiency and tolerance of crude enzyme for biocatalytic degradation of extremely high concentrations of aromatic pollutants than whole C. variabilis Sh42 cells. The monitored by-products indicated that the catabolic degradation pathway followed an oxidation mechanism via a site-specific monooxygenase enzyme. Benzoic acid and catechol were identified as major intermediates in the biodegradation pathway of 2-HBP, which were then biodegraded through meta-cleavage to 2-hydroxymuconic semialdehyde. With time elapsed, the semialdehyde product was further biodegraded to acetaldehyde and pyruvic acid, which would be further metabolized via the bacterial TCA cycle. CONCLUSION: The batch enzymatic bioreactors performed superior-specific biocatalytic degradation rates for all the studied xenobiotic pollutants. SIGNIFICANCE AND IMPACT OF THE STUDY: The enzymatic system of C. variabilis Sh42 is tolerable for toxic xenobiotics and different physicochemical environmental parameters. Thus, it can be recommended as an effective biocatalyst for biocatalytic remediation of xenobiotics polluted seawater.

Development of a generic lifelong physiologically based biokinetic model for exposome studies.

The current study within the frame of the HEALS project aims at the development of a lifelong physiologically based biokinetic (PBBK) model for exposome studies. The aim was to deliver a comprehensive modelling framework for addressing a large chemical space. Towards this aim, the delivered model can easily adapt parameters from existing ad-hoc models or complete the missing compound specific parameters using advanced quantitative structure activity relationship (QSAR). All major human organs are included, as well as arterial, venous, and portal blood compartments. Xenobiotics and their metabolites are linked through the metabolizing tissues. This is mainly the liver, but also other sites of metabolism might be considered (intestine, brain, skin, placenta) based on the presence or not of the enzymes involved in the metabolism of the compound of interest. Each tissue is described by three mass balance equations for (a) red blood cells, (b) plasma and interstitial tissue and (c) cells respectively. The anthropometric parameters of the models are time dependent, so as to provide a lifetime internal dose assessment, as well as to describe the continuously changing physiology of the mother and the developing fetus. An additional component of flexibility is that the biokinetic processes that relate to metabolism are related with either Michaelis-Menten kinetics, as well as intrinsic clearance kinetics. The capability of the model is demonstrated in the assessment of internal exposure and the prediction of expected biomonitored levels in urine for three major compounds within the HEALS project, namely bisphenol A (BPA), Bis(2-ethylhexyl) phthalate (DEHP) and cadmium (Cd). The results indicated that the predicted urinary levels fit very well with the ones from human biomonitoring (HBM) studies; internal exposure to plasticizers is very low (in the range of ng/L), while internal exposure to Cd is in the range of µg/L.

Uncertainty analysis in internal dose calculations for cerium considering the uncertainties of biokinetic parameters and S values.

Radioactive cerium and other lanthanides can be transported through the aquatic system into foodstuffs and then be incorporated by humans. Information on the uncertainty of reported dose coefficients for exposed members of the public is then needed for risk analysis. In this study, uncertainties of dose coefficients due to the ingestion of the radionuclides 141Ce and 144Ce were estimated. According to the schema of internal dose calculation, a general statistical method based on the propagation of uncertainty was developed. The method takes into account the uncertainties contributed by the biokinetic models and by the so-called S values. These S-values were derived by using Monte Carlo radiation transport simulations with five adult non-reference voxel computational phantoms that have been developed at Helmholtz Zentrum München, Germany. Random and Latin hypercube sampling techniques were applied to sample parameters of biokinetic models and S values. The uncertainty factors, expressed as the square root of the 97.5th and 2.5th percentile ratios, for organ equivalent dose coefficients of 141Ce were found to be in the range of 1.2-5.1 and for 144Ce in the range of 1.2-7.4. The uncertainty factor of the detriment-weighted dose coefficient for 141Ce is 2.5 and for 144Ce 3.9. It is concluded that a general statistical method for calculating the uncertainty of dose coefficients was developed and applied to the lanthanide cerium. The dose uncertainties obtained provide improved dose coefficients for radiation risk analysis of humans. Furthermore, these uncertainties can be used to identify those parameters most important in internal dose calculations by applying sensitivity analyses.