Calculation of internal dose from ingested soil-derived uranium in humans: Application of a new method.

The aim of the present study was to determine the internal dose in humans after the ingestion of soil highly contaminated with uranium. Therefore, an in vitro solubility assay was performed to estimate the bioaccessibility of uranium for two types of soil. Based on the results, the corresponding bioavailabilities were assessed by using a recently published method. Finally, these bioavailability data were used together with the biokinetic model of uranium to assess the internal doses for a hypothetical but realistic scenario characterized by a daily ingestion of 10 mg of soil over 1 year. The investigated soil samples were from two former uranium mining sites of Germany with (238)U concentrations of about 460 and 550 mg/kg. For these soils, the bioavailabilities of (238)U were quantified as 0.18 and 0.28 % (geometric mean) with 2.5th percentiles of 0.02 and 0.03 % and 97.5th percentiles of 1.48 and 2.34 %, respectively. The corresponding calculated annual committed effective doses for the assumed scenario were 0.4 and 0.6 µSv (GM) with 2.5th percentiles of 0.2 and 0.3 µSv and 97.5th percentiles of 1.6 and 3.0 µSv, respectively. These annual committed effective doses are similar to those from natural uranium intake by food and drinking water, which is estimated to be 0.5 µSv. Based on the present experimental data and the selected ingestion scenario, the investigated soils-although highly contaminated with uranium-are not expected to pose any major health risk to humans related to radiation.

Discrimination of cancerous and non-cancerous cell lines by headspace-analysis with PTR-MS.

Proton transfer reaction mass spectrometry (PTR-MS) has been used to analyze the volatile organic compounds (VOCs) emitted by in-vitro cultured human cells. For this purpose, two pairs of cancerous and non-cancerous human cell lines were selected:1. lung epithelium cells A-549 and retinal pigment epithelium cells hTERT-RPE1, cultured in different growth media; and 2. squamous lung carcinoma cells EPLC and immortalized human bronchial epithelial cells BEAS2B, cultured in identical growth medium. The VOCs in the headspace of the cell cultures were sampled: 1. online by drawing off the gas directly from the culture flask; and 2. by accumulation of the VOCs in PTFE bags connected to the flask for at least 12 h. The pure media were analyzed in the same way as the corresponding cells in order to provide a reference. Direct comparison of headspace VOCs from flasks with cells plus medium and from flasks with pure medium enabled the characterization of cell-line-specific production or consumption of VOCs. Among all identified VOCs in this respect, the most outstanding compound was m/z = 45 (acetaldehyde) revealing significant consumption by the cancerous cell lines but not by the non-cancerous cells. By applying multivariate statistical analysis using 42 selected marker VOCs, it was possible to clearly separate the cancerous and non-cancerous cell lines from each other.

Investigations on the activity concentrations of 238U, 226RA, 228RA, 210PB and 40K in Jordan phosphogypsum and fertilizers.

The activity concentrations of naturally occurring radionuclides ((238)U, (226)Ra, (228)Ra, (210)Pb and (40)K) in Jordanian phosphate ore, fertilizer material and phosphogypsum piles were investigated. The results show the partitioning of radionuclides in fertilizer products and phosphogypsum piles. The outcome of this study will enrich the Jordanian radiological map database, and will be useful for an estimation of the radiological impact of this industrial complex on the immediate environment. The activity concentration of (210)Pb was found to vary from 95 +/- 8 to 129 +/- 8 Bq kg(-1) with a mean value of 111 +/- 14 Bq kg(-1) in fertilizer samples, and from 364 +/- 8 to 428 +/- 10 Bq kg(-1) with a mean value of 391 +/- 30 Bq kg(-1) in phosphogypsum samples; while in phosphate wet rock samples, it was found to vary between 621 +/- 9 and 637 +/- 10 Bq kg(-1), with a mean value of 628 +/- 7 Bq kg(-1). The activity concentration of (226)Ra in fertilizer samples (between 31 +/- 4 and 42 +/- 5 Bq kg(-1) with a mean value of 37 +/- 6 Bq kg(-1)) was found to be much smaller than the activity concentration of (226)Ra in phosphogypsum samples (between 302 +/- 8 and 442 +/- 8 Bq kg(-1) with a mean value of 376 +/- 62 Bq kg(-1)). In contrast, the activity concentration of (238)U in fertilizer samples (between 1011 +/- 13 and 1061 +/- 14 Bq kg(-1) with a mean value of 1033 +/- 22 Bq kg(-1)) was found to be much higher than the activity concentration of (238)U in phosphogypsum samples (between 14 +/- 5 and 37 +/- 7 Bq kg(-1) with a mean value of 22 +/- 11 Bq kg(-1)). This indicates that (210)Pb and (226)Ra show similar behaviour, and are concentrated in phosphogypsum piles. In addition, both isotopes enhanced the activity concentration in phosphogypsum piles, while (238)U enhanced the activity concentration in the fertilizer. Due to the radioactivity released from the phosphate rock processing plants into the environment, the highest collective dose commitment for the lungs was found to be 1.02 person nGy t(-1). Lung tissue also shows the highest effect due the presence of (226)Ra in the radioactive cloud (0.087 person nGy t(-1)).

Measurements of daily urinary uranium excretion in German peacekeeping personnel and residents of the Kosovo region to assess potential intakes of depleted uranium (DU).

Following the end of the Kosovo conflict, in June 1999, a study was instigated to evaluate whether there was a cause for concern of health risk from depleted uranium (DU) to German peacekeeping personnel serving in the Balkans. In addition, the investigations were extended to residents of Kosovo and southern Serbia, who lived in areas where DU ammunitions were deployed. In order to assess a possible DU intake, both the urinary uranium excretion of volunteer residents and water samples were collected and analysed using inductively coupled plasma-mass spectrometry (ICP-MS). More than 1300 urine samples from peacekeeping personnel and unexposed controls of different genders and age were analysed to determine uranium excretion parameters. The urine measurements for 113 unexposed subjects revealed a daily uranium excretion rate with a geometric mean of 13.9 ng/d (geometric standard deviation (GSD)=2.17). The analysis of 1228 urine samples from the peacekeeping personnel resulted in a geometric mean of 12.8 ng/d (GSD=2.60). It follows that both unexposed controls and peacekeeping personnel excreted similar amounts of uranium. Inter-subject variation in uranium excretion was high and no significant age-specific differences were found. The second part of the study monitored 24 h urine samples provided by selected residents of Kosovo and adjacent regions of Serbia compared to controls from Munich, Germany. Total uranium and isotope ratios were measured in order to determine DU content. (235)U/(238)U ratios were within +/-0.3% of the natural value, and (236)U/(238)U was less than 2 x 10(-7), indicating no significant DU in any of the urine samples provided, despite total uranium excretion being relatively high in some cases. Measurements of ground and tap water samples from regions where DU munitions were deployed did not show any contamination with DU, except in one sample. It is concluded that both peacekeeping personnel and residents serving or living in the Balkans, respectively, were not exposed to significant amounts of DU.

Observation of changes in urinary excretion of thorium in humans following ingestion of a therapeutic soil.

The study investigated the changes in urinary thorium excretion by humans following ingestion of a therapeutic soil, which contains about 10 ppm of thorium. This well-known healing earth in Germany has been considered as an alternative medicine for diarrhoea and gastric hyper-acidity. Six adult volunteers ingested this therapeutic soil in varying quantities for 1-15 days at levels approximating those described in the package insert of the medicine (10-60 g of soil per day). The subjects ingested about 0.1-0.6 mg of thorium daily, which is 100-600 times higher than the normal daily intake of about 1 microg thorium in Germany. All 24-h urine samples collected from the subjects during pre-ingestion, ingestion and post-ingestion periods of the soil were analyzed for (232)Th using inductively coupled plasma mass spectrometry (ICP-MS). The measured excretion values varied in a wide range. Apparently, the high thorium amounts administered did not increase the (232)Th excretion in urine as expected, suggesting that this soil ingestion will not result in a considerably higher and harmful uptake of thorium into the human body.

Biokinetic modelling of natural thorium in humans by ingestion.

The retention of naturally occurring thorium (228Th, 230Th, 232Th) in model compartments and its daily urinary and faecal excretion after acute and chronic injections and ingestions were calculated for male and female subjects of six age groups based on the current age-dependent biokinetic model for thorium (Th) recommended by the International Commission on Radiological Protection (ICRP). The results are tabulated in a database. The calculated contents of 228,230,232Th in organs or tissues using their reference concentrations in foodstuffs for the European population are compared with autopsy data. The model prediction of 232Th in whole body for a 50-year-old unexposed person is 22 mBq, 86% of that in skeleton, 9.7% in other soft tissues, 3.4% in liver, 0.7% in kidneys and 0.01% in blood. The modelling predicts lower contents of the natural Th isotopes in whole body, especially in blood compared with measured data for the unexposed public. Modelled 232Th daily urinary excretions are 5 to 10 times less than bio-assay data from the authors' own laboratory.

Daily uranium excretion in German peacekeeping personnel serving on the Balkans compared to ICRP model prediction.

An investigation was performed to assess a possible health risk of depleted uranium (DU) for residents and German peacekeeping personnel serving on the Balkans. In order to evaluate a possible DU intake, the urinary uranium excretions of volunteers were collected and analysed using inductively coupled plasma mass spectrometry (ICP-MS). In total, more than 1300 urine samples from soldiers, civil servants and unexposed controls of different genders and ages were analysed to determine uranium excretion parameters. All participating volunteers, aged 3-92 y, were grouped according to their gender and age for evaluation. The results of the investigation revealed no significant difference between the unexposed controls and the peacekeeping personnel. In addition, the geometric means of the daily urinary excretion in peacekeeping personnel, ranging from 3 to 23 ng d(-1) for different age groups, fall toward the lower end of renal uranium excretion values published for unexposed populations in literature. The measured data were compared with the International Commission on Radiological Protection prediction for the intake of natural uranium by unexposed members of the public. The two data sets are in good agreement, indicating that no relevant intake of additional uranium, either natural or DU, has appeared for German peacekeeping personnel serving on the Balkans.

Improvements in routine internal monitoring--an overview of the IDEA project.

The IDEA project aimed to improve the assessment of incorporated radionuclides through developments of advanced in vivo and bioassay monitoring techniques and making use of such enhancements for improvements in routine monitoring. Many of these findings are not new in the sense that they are being already employed in advanced laboratories or for specialised applications. The primary goal was to categorise those new developments regarding their potential and eligibility for the routine monitoring community. Attention has been given to in vivo monitoring techniques with respect to detector characteristics and measurement geometry to improve measurement efficiency with special attention to low energy gamma emitters. Calibration-specifically supported by or through methods of numerical simulation-have been carefully analysed to reduce overall measurement uncertainties and explore ways to accommodate the individual variability based on characteristic features of a given person. For bioassay measurements at low detection limits, inductively coupled plasma mass spectroscopy offers significant advantages both in accuracy, speed, and sample preparation. Specifically, the determination of U and Th in urine and the associated models have been investigated. Finally, the scientific achievements have been analysed regarding their potential to offer benefits for routine monitoring. These findings will be presented in greater detail in other papers at this conference, whereas this paper intends to give an overview and put both the scientific achievements as well as the derived benefits into perspective.

Implementation of bioassay methods to improve assessment of incorporated radionuclides.

The present work which was carried out in the framework of an EU project (IDEA: Internal Dosimetry-Enhancements in Application; Contract Number: FIKR CT2001 00164) shall provide commonly acceptable guidelines for optimum performance of ICP-MS measurements with focus on urinary measurements of uranium, thorium and actinides. From the results of this work it is recommended that, whenever feasible, 24 h urine sampling should be conducted to avoid large uncertainties in the quantitation of daily urinary excretion values. For storage, urine samples should be acidified and kept frozen before analysis. Measurement of total uranium in urine by ICP-MS at physiological levels (<10 ng.l(-1)) requires no sample preparation besides UV photolysis and/or dilution. For the measurement of thorium in urine by ICP-MS, it can be concluded, that salt removal from the urine samples is not recommended. For the measurement of actinides in urine it is shown that ICP-MS is well-suited and a good alternative to alpha-spectrometry for isotopes with T1/2>5x10(4) years. In general, ICP-MS measurements are an easy, fast and cost-saving methodology. New improved measuring techniques (HR-SF-ICP-MS) with detection limits in urine of 150 pg.l(-1) (1.9 microBq.l(-1)) for 238U, 30 pg.l(-1) (2.4 microBq.l(-1)) for 235U and 100 pg.l(-1) (0.4 microBq.l(-1)) for (232)Th, respectively, meet all necessary requirements. This method should therefore become the routine technique for incorporation monitoring of workers and of members of the general public, in particular for uranium contamination.

Practical implications of procedures developed in IDEA project--comparison with traditional methods.

The idea of the IDEA project aimed to improve assessment of incorporated radionuclides through developments of more reliable and possibly faster in vivo and bioassay monitoring techniques and making use of such enhancements for improvements in routine monitoring. In direct in vivo monitoring technique the optimum choice of the detectors to be applied for different monitoring tasks has been investigated in terms of material, size and background in order to improve conditions namely to increase counting efficiency and reduce background. Detailed studies have been performed to investigate the manifold advantageous applications and capabilities of numerical simulation method for the calibration and optimisation of in vivo counting systems. This calibration method can be advantageously applied especially in the measurement of low-energy photon emitting radionuclides, where individual variability is a significant source of uncertainty. In bioassay measurements the use of inductively coupled plasma mass spectrometry (ICP-MS) can improve considerably both the measurement speed and the lower limit of detection currently achievable with alpha spectrometry for long-lived radionuclides. The work carried out in this project provided detailed guidelines for optimum performance of the technique of ICP-MS applied mainly for the determination of uranium and thorium nuclides in the urine including sampling procedure, operational parameters of the instruments and interpretation of the measured data. The paper demonstrates the main advantages of investigated techniques in comparison with the performances of methods commonly applied in routine monitoring practice.

Measurement techniques for tracer kinetic studies with stable isotopes of zirconium.

Biokinetic models are used in radiation protection to assess internal radiation doses. Experiments with stable isotopes as tracers can be performed to obtain characteristic parameters of these models. Two methods for the measurement of zirconium isotopes in human biological samples are presented--thermal ionisation mass spectrometry (TIMS) and proton nuclear activation analysis (PNA). Descriptions include sample preparation, operating conditions, relative uncertainties and method detection limits as well as important properties of both methods.

Methods for assessing gastrointestinal absorption of strontium in humans by stable tracer techniques.

Intestinal absorption of strontium from an oral test dose was studied in 13 healthy human volunteers using double tracer techniques with two stable strontium isotopes as tracers. Defined amounts of one isotope were administered orally, while tracer amounts of the second isotope were injected intravenously. Two different methods were used to assess the total fraction absorbed (f1 value). Fractional intestinal strontium absorption can be calculated from the ratio of the two isotopes in plasma or urine samples (in this paper called the double-isotope method) or the convolution integral technique, since both methods provide an accurate estimate of fractional absorption and yield comparable results. The latter additionally provides information on the absorption kinetics in the gastrointestinal tract. The absorption varies with respect to the chemical form and to the amount administered. Absorption patterns are characteristically different for uptake from solutions or from whole meals.

Na(+)- and anion-dependent Mg2+ influx in isolated hepatocytes.

Hepatocytes, which were Mg(2+)-depleted during isolation, took up Mg2+ during reincubation. Mg2+ uptake was dependent on the concentration of extracellular Mg2+, Na+, Cl-, bicarbonate and phosphate. Li+ and choline+ did not substitute for extracellular Na+ in Mg2+ influx. Mg2+ influx was maximal when all three anion species were present, and did not occur when these anions were replaced by gluconate. Bicarbonate, phosphate and Cl- could substitute for each other. Mg2+ uptake in hepatocytes was inhibited by p-chloromercuribenzene sulfonate, ouabain, gramicidin D, amiloride and verapamil. The results were explained by the assumption that net Mg2+ influx in hepatocytes is operating via electroneutral Na+, Mg2+/anion cotransport driven by the Na+ gradient. However, electrogenic Mg2+ uptake gated by extracellular Na+ and anions could not be excluded.

Characterization of Na(+)-dependent Mg2+ efflux from Mg2(+)-loaded rat erythrocytes.

Na(+)-dependent Mg2+ efflux from Mg2(+)-loaded rat erythrocytes was determined from the increase of extracellular Mg2+ concentration or decrease of intracellular Mg2+ content, as measured by means of atomic absorption spectrophotometry. Mg2+ efflux was specifically combined with the uptake of Na+ at a stoichiometric ratio of 2Na+:1Mg2+, indicating electroneutral Na+/Mg2+ antiport. Na+/Mg2+ antiport depended on intracellular ATP and was inhibited by amiloride and quinidine, but was insensitive to strophanthin. Net Mg2+ efflux was only occurring at increased concentration of intracellular Mg2+ ([Mg2+]i), and stopped when the physiological Mg2+ content was reached. Intracellular Mg2+ acted cooperatively with a Hill coefficient of 2.4, which may indicate gating of Na+/Mg2+ antiport at increased [Mg2+]i. At increased intracellular Na+ concentration, Na+ competed with intracellular Mg2+ for Mg2+ efflux and Na+ could leave the rat erythrocyte via this transport system. Na+/Mg2+ antiport was working asymmetrically with respect to extra- and intracellular Na+ and Mg2+, and did not perform net Mg2+ uptake.

Validating an important aspect of the new ICRP biokinetic model of thorium.

The daily urinary excretion of Th (Th) was estimated in 11 adult German subjects who were not exposed occupationally to thorium and its related compounds. Thirty-one urine samples were collected over 24-h periods on different occasions from these subjects and were analyzed using high resolution sector field inductively coupled plasma mass spectrometry (HR-SF-ICP-MS). Using this instrument a limit of detection of 20 pg L for thorium in the reagent blank was achieved. The median (mean) daily urinary thorium excretion was obtained as 1.0 (1.8) ng. This was in good agreement with the mean value of 1.5 ng Th (6 microBq) reported by another group for German population, but is significantly lower in comparison to the daily excretion range of 3.6 to 105 ng reported from other countries. The expected daily urinary excretion of thorium for the adult German population was also calculated by applying the new ICRP biokinetic model of thorium assuming reference intake values. The expected urinary thorium excretion rate for this age group is about 0.1 ng per day. Even if a small contribution from the inhalation is considered, the calculated value will be much lower than the measured values. The reason for the disagreement appears to be the use of a low gastrointestinal absorption factor (f1) of 5 x 10 in the ICRP model. Based on the present study, a higher f1 factor might be proposed separately for dietary incorporated thorium.

Can default ICRP f1 values be applied to determine radiation dose from the intake of diet-incorporated thorium?

Data on the daily urinary excretion of thorium (Th) was obtained from 15 non-exposed adult German subjects. A radiochemical neutron activation analysis method was developed and standardised especially for this purpose. The daily urinary excretion of 232Th was found to be in the range 1.9-14.9 microBq d(-1) with a mean (+/-SD) value of 6.5 (+/-4.3) microBq d(-1). Using this excretion value and reported data on dietary intake of Th for a similar German population, the gastrointestinal absorption factor (f1 value) proposed by the International Commission on Radiological Protection (ICRP) was tested. Although the daily excretion of 232Th observed in the present study was comparable to some of the currently reported values in certain other countries, it was higher than the excretion value calculated by applying the biokinetic model of Th proposed by ICRP for the dietary intake values. The study showed that the default ICRP values of the f1 factor for diet-incorporated Th may not be applicable.

Isoproterenol-induced Mg2+ uptake in liver.

Isoproterenol increased the Mg2+ content of hepatocytes after injection into rats or after addition to collagenase-dispersed hepatocytes. cAMP also the increased cellular Mg2+ content of isolated hepatocytes. This effect was prevented by staurosporine. Phorbol ester had no effect on the Mg2+ content of isolated hepatocytes, and after injection of isoproterenol into rats, protein kinase C of liver was not affected. It was concluded that isoproterenol induced long-term Mg2+ influx via the activation of protein kinase A which can be inhibited by staurosporine.

Lipid peroxidation in mitochondria and microsomes from adult and fetal rat tissues. Effects of Zn deficiency, Fe, and salicylate.

Pregnant female Wistar rats that received a control (100 ppm Zn) or a Zn-deficient diet (1.5 ppm Zn) from d 0 to 21, or nonpregnant normally fed female rats without or with five daily oral doses of 300 mg/kg salicylic acid were used for the experiments. In isolated mitochondria or microsomes from various maternal and fetal tissues, lipid peroxidation was determined as malondialdehyde formation measured by means of the thiobarbiturate method. Zn deficiency increased lipid peroxidation in mitochondria and microsomes from maternal and fetal liver, maternal kidney, maternal lung microsomes, and fetal lung mitochondria. Lipid peroxidation in fetal microsomes was very low. Zn deficiency produced a further reduction of lipid peroxidation in fetal liver microsomes. Salicylate increased lipid peroxidation in liver mitochondria and microsomes after addition in vitro and after application in vivo. The increase of lipid peroxidation by salicylate may be caused by two mechanisms: an increased cellular Fe uptake that, in turn, can increase lipid peroxidation and chelating Fe, in analogy to the effect of ADP in lipid peroxidation. The latter effect of salicylate is particularly expressed at increased Fe content.

Effects of salicylate and zinc deficiency on the serum concentrations of magnesium, calcium, and parathyroid hormone.

Oral application of 700 mg/kg salicylic acid to pregnant and non-pregnant female rats caused an increase of serum Mg2+ and a decrease of serum Ca2+ concentration. The salicylate effect was drastically enhanced by Zn deficiency. The increase in serum Mg2+ is probably caused by the nephrotoxicity of salicylate. The decrease of serum Ca2+ concentration is combined with an increase of parathyroid hormone concentration in serum. Probably, salicylate and Zn deficiency inhibit Ca2+ mobilization by parathyroid hormone in bone.

Effect of valproate on zinc metabolism in fetal and maternal rats fed normal and zinc-deficient diets.

Pregnant Wistar rats fed control and Zn-deficient diets received daily oral doses of 0, 100, and 300 mg/kg sodium valproate from d 16 to 20 of gestation. Only the highest valproate doses induced a small reduction in fetal body weight in the normally fed group. Zinc deficiency caused a drastic reduction in maternal and only a small reduction in fetal serum Zn concentrations. Valproate treatment had no effect on maternal and fetal serum Zn concentrations.Valproate reduced fetal liver Zn content only in the normally fed group. The reduction of liver Zn content resulted from the reduction of Zn-metallothionein. Valproate did not affect total Zn and Zn-metallothionein in kidneys. Three percent of the Zn-deficient fetuses developed hydronephrosis and hydrops. Valproate treatment drastically enhanced the occurrence of fetal hydronephrosis and hydrops. Valproate induced fetal liver necroses, independent of Zn nutrition.