Hydrogen-rich water attenuates the radiotoxicity induced by tritium exposure in vitro and in vivo.

Radionuclide tritium is widely used in the nuclear energy production industry and creates a threat to human health through radiation exposure. Herein, the radioactive elimination and radioprotective effect of hydrogen-rich water (HRW), a potential antioxidant with various medical applications, on tritiated water (HTO) exposure, was studied in vitro and in vivo. Results showed that intragastric administration of HRW effectively promoted the elimination of urinary tritium, decreased the level of serum tritium and tissue-bound tritium (OBT), and attenuated the genetic damage of blood cells in mice exposed to HTO (18.5 MBq/kg). Pretreatment with HRW effectively reduces tritium accumulation in HTO-treated human blood B lymphocyte AHH-1 cells. In addition, the anti-oxidative properties of HRW could attenuate the increased intracellular ROS (such as O2•-, •OH and ONOO-), resulting in reversing the exhaustion of cellular endogenous antioxidants (reduced GSH and SOD), decreasing lipid peroxidation (MDA), relieving DNA oxidative damage, and depressing cell apoptosis and cytotoxicity induced by HTO exposure. In conclusion, HRW is expected to be an effective radioactive elimination agent through the competition effect of isotope exchange or a radioprotective agent by scavenging free radicals induced by HTO exposure.

Determination of tritium concentrations in humans before the development of a nuclear power plant in Turkey.

The most widely used method to determine the level of tritium in humans is testing urine. Tritium concentrations in urine samples of 100 persons aged 18-66 years selected randomly from a pilot region in Turkey were analysed. The average activity concentration of urine samples was 4.66 ± 1.94 Bq L(-1) and the maximum activity concentration was 27.91 Bq L(-1). The minimum detectable activity was 2.38 Bq L(-1). The annual effective dose from tritium was also evaluated on the basis of the measurement results and reference values recommended by the International Commission on Radiological Protection. The effective doses for males and females were 4.56 and 3.54 nSv, respectively. These results were lower than the permissible annual effective dose for members of the public.

Determination of total tritium in urine from residents living in the vicinity of nuclear power plants in Qinshan, China.

To estimate the tritium doses of the residents living in the vicinity of a nuclear power plant, urine samples of 34 adults were collected from residents living near the Qinshan nuclear power plant. The tritium-in-urine (HTO plus OBT) was measured by liquid scintillation counting. The doses of tritium-in-urine from participants living at 2, 10 and 22 km were in a range of 1.26-6.73 Bq/L, 1.31-3.09 Bq/L and 2.21-3.81 Bq/L, respectively, while the average activity concentrations of participants from the three groups were 3.53 ± 1.62, 2.09 ± 0.62 and 2.97 ± 0.78 Bq/L, respectively. The personal committed effective doses for males were 2.5 ± 1.7 nSv and for females they were 2.9 ± 1.3 nSv. These results indicate that tritium concentrations in urine samples from residents living at 2 km from a nuclear power plant are significantly higher than those at 10 km. It may be the downwind direction that caused a higher dose in participants living at 22 km. All the measured doses of tritium-in-urine are in a background level range.

Tritium analysis of urine samples from the general Korean public.

The tritium concentrations of urine samples and the effective dose of the general Korean public were evaluated. To achieve accurate HTO analysis of urine samples, we established the optimal conditions for measuring the HTO content of urine samples. Urine samples from 50 Koreans who do not work at a nuclear facility were analyzed on the basis of the results. The average urine analysis result was 2.8 ±1 .4 Bq/L, and the range was 1.8-5.6 Bq/L. The measured values were lower than those reported for other countries. These results show that environmental factors and lifestyle differences are the main factors affecting the tritium level of the general public.

Retention and excretion of ³H in rats following the intratracheal intubation of tritiated pump oil.

Saturated hydrocarbon mineral oils in vacuum pumps used in ³H handling facilities often contain significant amounts of ³H (as much as several hundred GBq L⁻¹), and during maintenance the air around an open pump may contain MBq L of volatile and aerosol species. It follows that H-contaminated pump oils pose a workplace hazard-especially if inhaled deposits are retained in the lung. A long-term study (1-y duration) was undertaken to establish the retention time of ³H-pump oil in the lungs of rats. Excretion data was collected to establish the mechanism of oil clearance from the lung. Finally, liver data was collected both to indicate the levels of H in the rat body and to indicate either the presence or absence of the transfer of unmetabolized pump oil within cells from the lungs to liver. Within 1 d following intubation into the trachea, ∼16.5% of the emulsified pump oil had been rapidly mechanically cleared to feces, and 1.1%, present as HTO, or exchangeable H, was excreted in urine. 69.4% of the instilled dose remained in the lungs as the initial alveolar burden. Subsequently, H cleared from the lungs with a retention half-time of of 223 d. The lung burden was mostly cleared to feces-indicating that the pump oil droplets remaining in the lungs were behaving like insoluble particles, but the kinetics of clearance of particles and oil droplets may be different. Overall, it is concluded that inhaled H-pump oil should most likely be regarded as an insoluble particulate (ICRP Inhalation Type S) for the purposes of radiological protection dosimetry, but the possibility of Type M behavior cannot be excluded.

An analysis of workers' tritium concentration in urine samples as a function of time after intake at Korean pressurised heavy water reactors.

In general, internal exposure from tritium at pressurised heavy water reactors (PHWRs) accounts for ∼20-40 % of the total radiation dose. Tritium usually reaches the equilibrium concentration after a few hours inside the body and is then excreted from the body with an effective half-life in the order of 10 d. In this study, tritium metabolism was reviewed using its excretion rate in urine samples of workers at Korean PHWRs. The tritium concentration in workers' urine samples was also measured as a function of time after intake. On the basis of the monitoring results, changes in the tritium concentration inside the body were then analysed.

Liquid scintillation based quantitative measurement of dual radioisotopes (3H and 45Ca) in biological samples for bone remodeling studies.

Acute and prolonged bone complications associated with radiation and chemotherapy in cancer survivors underscore the importance of establishing a laboratory-based complementary dual-isotope tool to evaluate short- as well as long-term bone remodeling in an in vivo model. To address this need, a liquid scintillation dual-label method was investigated using different scintillation cocktails for quantitative measurement of (3)H-tetracycline ((3)H-TC) and (45)Ca as markers of bone turnover in mice. Individual samples were prepared over a wide range of known (45)Ca/(3)H activity ratios. Results showed that (45)Ca/(3)H activity ratios determined experimentally by the dual-label method were comparable to the known activity ratios (percentage difference ∼2%), but large variations were found in samples with (45)Ca/(3)H activity ratios in range of 2-10 (percentage difference ∼20-30%). Urine and fecal samples from mice administered with both (3)H-TC and (45)Ca were analyzed with the dual-label method. Positive correlations between (3)H and (45)Ca in urine (R=0.93) and feces (R=0.83) indicate that (3)H-TC and (45)Ca can be interchangeably used to monitor longitudinal in vivo skeletal remodeling.

Preparation and application of tea to a tritium performance testing programme.

A simple, but novel technique, for adjusting steeps of black tea to produce fluids, which are visually and spectroscopically similar to urine, has been developed at the National Calibration Reference Centre for Bioassay and In Vivo Monitoring in Canada. The method uses scans of absorbance versus wavelength, in the UV-VIS range (200-800 nm) to select diluted tea steeps that simulate urine. Tea solutions (1 and 10 %) were spiked with tritium and distributed to laboratories for performance testing (PT). The PT exercise was done as in a regular bioassay programme. The results showed that all samples satisfied the pass/fail conditions of the S-106 standard of the Canadian Nuclear Safety Commission, suggesting that adjusted tea successfully simulated urine for the tritium PT programmes. Also, since unlike urine whose use may increase the probability of contaminating and transmitting diseases (e.g. hepatitis C), tea is a safer alternative. When needed, it can readily be prepared for the laboratories.

Analysis of urine for pure beta emitters: methods and application.

Bioassay for individual radionuclides is an essential and first step in estimation of radiation risk to nuclear facilities workers and people who are exposed to the contaminated environment in the event of a nuclear accident or radiological attack. Urine is a frequently used biological sample for this purpose. Tritium and (14)C are important radionuclides for workers in nuclear reactors and radiopharmaceutical laboratories. A method for the determination of tritium and (14)C in organic and inorganic forms in urine has been developed. It involves activated charcoal absorption of organic matter followed by combustion to separate tritiated water from organically-bound tritium. Inorganic (14)C from organically-bound (14)C, the separated tritium and (14)C were measured using liquid scintillation counting. Iodine-129, a long-lived beta emitter, is normally released to the atmosphere during the operation of nuclear facilities, especially in reprocessing plants. The high concentration of iodine in the thyroid makes this radionuclide an important source of exposure to exposed populations. A simple method has been developed in this work for the determination of (129)I in urine by anion exchange preconcentration, extraction purification and liquid scintillation counting. Using accelerator mass spectrometry, urine samples can be analyzed for low level (129)I in both organic and inorganic forms after active charcoal adsorption and solvent extraction separation. Condensed water collected daily from the reactor hall in a Danish research reactor and monthly urine samples from the staff working in the reactor building were collected from 2003-2010 and analyzed using this method, and the results are presented and discussed.

Estimation of biological half-life of tritium in coastal region of India.

The present study estimates biological half-life (BHL) of tritium by analysing routine bioassay samples of radiation workers. During 2007-2009 year, 72,100 urine bioassay samples of the workers were analysed by liquid scintillation counting technique for internal dose monitoring for tritium. Two hundred and two subjects were taken for study with minimum 3 µCiL(-1) tritium uptake in their body fluid. The BHL of tritium of subjects ranges from 1 to 16 d with an average of 8.19 d. Human data indicate that the biological retention time ranges from 4 to 18 d with an average of 10 d. The seasonal variations of the BHL of tritium are 3.09 ± 1.48, 6.87 ± 0.58 and 5.73 ± 0.76 d (mean ± SD) for summer, winter and rainy seasons, respectively, for free water tritium in the coastal region of Karnataka, India, which shows that the BHL in summer is twice that of the winter season. Also three subjects showed the BHL of 101.73-121.09 d, which reveals that organically bound tritium is present with low tritium uptake also. The BHL of tritium for all age group of workers is observed independent of age and is shorter during April to May. The distribution of cumulative probability vs. BHL of tritium shows lognormal distribution with a geometric mean of 9.11 d and geometric standard deviation of 1.77 d. The study of the subjects is fit for two-compartment model and also an average BHL of tritium is found similar to earlier studies.

Bone seeking labels as markers for bone turnover: effect of dosing schedule on labeling various bone sites in rats.

Urinary excretion of bone labels can be used to monitor bone resorption. Here we investigate the effects of dosing frequency on label incorporation of various sites when bone turnover was perturbed by ovariectomy. We compared tritiated tetracycline ((3)H-TC) and (45)Ca in two studies. Nine-month-old rats were given single or multiple injections of (3)H-TC and (45)Ca and sacrificed after 7 or 14 days. Six-month-old OVX rats were given (3)H-TC and (41)Ca tracers 1 or 3 months following ovariectomy (OVX + 1 mo or OVX + 3 mo, when bone turnover was higher or lower, respectively) and sacrificed 1 week, 1 month, 3 months, or 6 months postdose. Twenty-four-hour urine pools over 2-4 consecutive days as well as the proximal tibia, femur midshaft, lumbar vertebrae (L1-L4), and remaining skeleton were analyzed for (3)H, (45)Ca, and calcium content. Bone turnover as assessed by urinary (3)H-TC was greater in OVX + 1 mo compared to OVX + 3 mo rats up to 6 months postdose. (45)Ca labeling efficiency (% dose/g Ca) was significantly higher than for (3)H and labeling was higher in trabecular-rich than cortical-rich bone. This study affirms that a single administration of either (3)H-TC or (45)Ca is a useful approach to measuring bone turnover directly. The amount of label incorporation into bone was greater in bone sites that were more metabolically active and in all sites when closer vs farther from OVX.

A non-invasive technique for analyzing fecal cortisol metabolites in snowshoe hares (Lepus americanus).

To develop non-invasive techniques for monitoring steroid stress hormones in the feces of free-living animals, extensive knowledge of their metabolism and excretion is essential. Here, we conducted four studies to validate the use of an enzyme immunoassay for monitoring fecal cortisol metabolites in snowshoe hares (Lepus americanus). First, we injected 11 hares with radioactive cortisol and collected all voided urine and feces for 4 days. Radioactive metabolites were recovered predominantly in the urine (59%), with only 8% recovered in the feces. Peak radioactivity was detected an average of 3.5 and 5.7 h after injection in the urine and feces, respectively. Second, we investigated diurnal rhythms in fecal cortisol metabolites by measuring recovered radioactivity 2 days after the radioactive cortisol injection. The total amount of radioactivity recovered showed a strong diurnal rhythm, but the amount of radioactivity excreted per gram of feces did not, remaining constant. Third, we injected hares with dexamethasone to suppress fecal cortisol metabolites and 2 days later with adrenocorticotropic hormone to increase fecal cortisol metabolites. Dexamethasone decreased fecal cortisol metabolites concentrations by 61% and adrenocorticotropic hormone increased them by 1,000%, 8-12 h after injection. Fourth, we exposed hares to a simulated predator (dog). This increased the fecal cortisol metabolites concentrations by 175% compared with baseline concentrations 8-12 h after exposure. Thus, this enzyme immunoassay provides a robust foundation for non-invasive field studies of stress in hares.

Internal dose assessments: uncertainty studies and update of ideas guidelines and databases within CONRAD project.

The work of Task Group 5.1 (uncertainty studies and revision of IDEAS guidelines) and Task Group 5.5 (update of IDEAS databases) of the CONRAD project is described. Scattering factor (SF) values (i.e. measurement uncertainties) have been calculated for different radionuclides and types of monitoring data using real data contained in the IDEAS Internal Contamination Database. Based upon this work and other published values, default SF values are suggested. Uncertainty studies have been carried out using both a Bayesian approach as well as a frequentist (classical) approach. The IDEAS guidelines have been revised in areas relating to the evaluation of an effective AMAD, guidance is given on evaluating wound cases with the NCRP wound model and suggestions made on the number and type of measurements required for dose assessment.

Screening methods for estimating tritium dose.

Tritium intake may occur in certain workplaces by design or by accident. If the health physics staff has developed a formal bioassay program, then it is likely that dose estimates from tritium intake are readily determinable. However, in the case of tritium intake at a facility where no formal program exists, it may be necessary to make simple confirmatory estimates of dose due to tritium exposure. Lifetime dose estimates may be calculated by using data from urine samples taken over a period of time. If urine data are unavailable, estimates of committed dose equivalent may be made with air sample data and knowledge of workplace activities.

Tritium in the urine in Finnish people.

Tritium in urine was analysed from 227 randomly selected Finnish adults. The people were 18 to 65 of age. Urine samples were collected over night. The mean activity concentration of tritiated water in urine was 2.5 Bq l(-1) and the maximum activity concentration 18.3 Bq l(-1). The minimum detectable activity varied from 1.5 to 2.3 Bq l(-1). Because organically bound tritium is approximately 10% of the total tritium, its concentration was below the detection limit and could be ignored. The mean effective dose for Finnish people from tritium was 2.4 x 10(-3) microSv y(-1).

An improved method for Organic Bound Tritium (OBT) determination in urine samples.

The Organic Bound Tritium (OBT) amount in the body may induce changes in the evaluation of the internal exposure to tritium, due to its different retention time relative to HTO. OBT measurements for urine are not performed routinely, mainly because of the lengthy work needed in preparation of the samples, when using the standard oxygen combustion method. A simpler and more rapid method based on liquid scintillation counting (LSC) was employed, and an evaluation was performed to check its suitability for urine samples. The principle of the proposed method is based on subtracting the LSC counts of the water phase sample (HTO) from the total activity of the urine sample (OBT+HTO). A good correlation was found between the results obtained when applying the proposed direct method and the Gold standard method. The minimum detectable activity when using this method was determined.

Non-invasive measurement of small peptides in the common marmoset (Callithrix jacchus): a radiolabeled clearance study and endogenous excretion under varying social conditions.

A non-invasive assay for measurement of oxytocin (OT) and vasopressin (AVP) in primates would enable researchers to study the relationship between the endocrine system and behavior without disturbing potentially endangered animals in their natural habitats. In order to test whether or not OT specifically would be measurable in the urine of a primate, 10 microCi of tritium-labeled OT were injected into the peripheral blood supply of four adult male common marmosets (Callithrix jacchus), with continuous urinary collection over 48 h. When urine was processed by HPLC separation and beta counting for radioactive clearance, the label was present in all samples in the fraction where OT elutes. Large amounts of OT were also seen in a fraction other than that containing the OT standard, indicating that OT is measurable but that it also undergoes substantial metabolic breakdown. In a second experiment, we isolated six common marmosets for 48 h and then exposed them to social contact to evaluate the effect of changing social stimuli on endogenous urinary measurement of both OT and AVP. Both were measured after HPLC separation to isolate the intact molecule and also to control for cross-reactivity with metabolites in subsequent RIA. Cortisol was also measured to objectively evaluate the stress response. A priori assumptions were that urinary OT and AVP would be lower during a period of isolation and higher during periods of social contact. These assumptions were met, leading us to conclude that peripheral OT and AVP are measurable via urinary assay and that such an assay is a valid means of evaluating social condition in this species.

Buprenorphine duration of action: mu-opioid receptor availability and pharmacokinetic and behavioral indices.

BACKGROUND: Buprenorphine (BUP) is effective in the treatment of opioid dependence when given on alternating days, probably as a result of long-lasting occupation of micro opioid receptors (microORs). This study examined the duration of action of BUP at microORs and correlations with pharmacokinetic and pharmacodynamic outcomes in 10 heroin-dependent volunteers. METHODS: Availability of microOR (measured with positron emission tomography and [(11)C]-carfentanil), plasma BUP concentration, opioid withdrawal symptoms, and blockade of hydromorphone (HYD; heroin-like agonist) effects were measured at 4, 28, 52, and 76 hours after omitting the 16 mg/d dose of BUP in a study reported elsewhere. RESULTS: Relative to heroin-dependent volunteers maintained on BUP placebo, whole-brain microOR availability was 30%, 54%, 67%, and 82% at 4, 28, 52, and 76 hours after BUP. Regions of interest showed similar effects. Plasma concentrations of BUP were time dependent, as were withdrawal symptoms, carbon dioxide sensitivity and extent of HYD blockade. Availability of microOR was also correlated with BUP plasma concentration, withdrawal symptoms, and HYD blockade. CONCLUSIONS: Together with our previous findings, it appears that microOR availability predicts changes in pharmacokinetic and pharmacodynamic measures and that about 50%-60% BUP occupancy is required for adequate withdrawal symptom suppression (in the absence of other opioids) and HYD blockade.

The in vivo degradation, absorption and excretion of PCL-based implant.

The in vivo degradation of poly (epsilon-caprolactone)(PCL) was observed for 3 years in rats. The distribution, absorption and excretion of PCL were traced in rats by radioactive labeling. The results showed that PCL capsules with initial molecular weight (Mw) of 66000 remained intact in shape during 2-year implantation. It broke into low molecular weight (Mw=8000) pieces at the end of 30 months. The Mw of PCL deceased with time and followed a linear relationship between logMw and time. Tritium-labeled PCL (Mw 3000) was subcutaneous implanted in rats to investigate its absorption and excretion. The radioactive tracer was first detected in plasma 15 days after implantation. At the same time radioactive excreta was recovered from feces and urine. An accumulative 92% of the implanted radioactive tracer was excreted from feces and urine by 135 days after implantation. In the mean while, the plasma radioactivity dropped to the background level. Radioactivity in the organs was all close to the background level confirming that the material did not cumulate in body tissue and could be completely excreted.