Study of charged particle activation analysis (II): Determination of boron concentration in human blood samples.

Boron Neutron Capture Therapy (BNCT) is a radiotherapy for the treatment of intractable cancer. In BNCT precise determination of 10B concentration in whole blood sample before neutron irradiation of the patient, as well as accurate neutron dosimetry, is crucial for control of the neutron irradiation time. For this purpose ICP-AES and neutron induced prompt γ-ray analysis are generally used. In Ibaraki Neutron Medical Research Center (iNMRC), an intense proton beam will be accelerated up to 8 MeV, which can also be used for Charged Particle Activation Analysis (CPAA). Thus, in this study, we apply the CPAA utilizing the proton beam to non-destructive and accurate determination of 10B concentration in whole blood sample. A CPAA experiment is performed by utilizing an 8 MeV proton beam from the tandem accelerator of Nuclear Science Research Institute in Japan Atomic Energy Agency. The 478 keV γ-ray of 7Be produced by the 10B(p, α)7Be reaction is used to quantify the 10B in human blood. The 478 keV γ-ray intensity is normalized by the intensities of the 847 keV and 1238 keV γ-rays of 56Co originating from Fe in blood. The normalization methods were found to be linear in the range of 3.27 µg 10B/g to 322 µg 10B/g with correlation coefficients of better than 0.9999.

Extending neutron autoradiography technique for boron concentration measurements in hard tissues.

The neutron autoradiography technique using polycarbonate nuclear track detectors (NTD) has been extended to quantify the boron concentration in hard tissues, an application of special interest in Boron Neutron Capture Therapy (BNCT). Chemical and mechanical processing methods to prepare thin tissue sections as required by this technique have been explored. Four different decalcification methods governed by slow and fast kinetics were tested in boron-loaded bones. Due to the significant loss of the boron content, this technique was discarded. On the contrary, mechanical manipulation to obtain bone powder and tissue sections of tens of microns thick proved reproducible and suitable, ensuring a proper conservation of the boron content in the samples. A calibration curve that relates the 10B concentration of a bone sample and the track density in a Lexan NTD is presented. Bone powder embedded in boric acid solution with known boron concentrations between 0 and 100 ppm was used as a standard material. The samples, contained in slim Lexan cases, were exposed to a neutron fluence of 1012 cm-2 at the thermal column central facility of the RA-3 reactor (Argentina). The revealed tracks in the NTD were counted with an image processing software. The effect of track overlapping was studied and corresponding corrections were implemented in the presented calibration curve. Stochastic simulations of the track densities produced by the products of the 10B thermal neutron capture reaction for different boron concentrations in bone were performed and compared with the experimental results. The remarkable agreement between the two curves suggested the suitability of the obtained experimental calibration curve. This neutron autoradiography technique was finally applied to determine the boron concentration in pulverized and compact bone samples coming from a sheep experimental model. The obtained results for both type of samples agreed with boron measurements carried out by ICP-OES within experimental uncertainties. The fact that the histological structure of bone sections remains preserved allows for future boron microdistribution analysis.

Boron concentration in water, sediment and different organisms around large borate deposits of Turkey.

Boron is an essential nutrient for plants and an essential element for many organisms, but can be toxic to aquatic and terrestrial organisms above certain concentrations. The aim of this research was to determine boron concentrations in water, sediment and biotic samples (Gammaridae spp.-Crustacea, Helix sp.-Gastropoda, Donax sp.-Bivalvia, Helobdella sp.-Hirudinae, Ephemeroptera nymph, Chrinomidae larvae, Tipulidae larvae-Insecta, Rana sp.-Amphibia, Natrix sp.-Serpentes, fish sample Leiscus cephalus (Linnaeus, 1758) and leaves of Salix sp.-Salicacea from Seydi Stream (Kirka-Eskisehir). Our results have shown that boron concentrations of the Seydi Stream water is higher than the Turkish Environmental Guidelines standard (>1 mg L(-1)) and in Europe (mean values typically below 0.6 mg L(-1)).

Applications of mechanistic data in risk assessment: the past, present, and future.

Mechanistic data, when available, have long been considered in risk assessment, such as in the development of the nitrate RfD based on effects in a sensitive group (infants). Recent advances in biology and risk assessment methods have led to a tremendous increase in the use of mechanistic data in risk assessment. Toxicokinetic data can improve extrapolation from animals to humans and characterization of human variability. This is done by the development of improved tissue dosimetry, by the use of uncertainty factors based on chemical-specific data, and in the development of physiologically based pharmacokinetic (PBPK) models. The development of the boron RfD illustrates the use of chemical-specific data in the improved choice of uncertainty factors. The draft cancer guidelines of the U.S. Environmental Protection Agency emphasize the use of mode of action data. The first choice under the guidelines is to use a chemical-specific, biologically based dose-response (BBDR) model. In the absence of a BBDR model, mode of action data are used to determine whether low-dose extrapolation is done using a linear or nonlinear (margin of exposure) approach. Considerations involved in evaluating a hypothesized mode of action are illustrated using 1,3-dichloropropene, and use of a BBDR model is illustrated using formaldehyde. Recent developments in molecular biology, including transgenic animals, microarrays, and the characterization of genetic polymorphisms, have significant potential for improving risk assessments, although further methods development is needed. Overall, use of mechanistic data has significant potential for reducing the uncertainty in assessments, while at the same time highlighting the areas of uncertainty.

Considerations in the determination of boron at low concentrations.

Experimental evidence now supports the nutritional essentiality of boron (B) in some biological systems, and accordingly, the need for reliable analytical B data is increasing. However, the accurate determination of B in biological materials is a formidable challenge at low concentrations (<1 mg B/kg). Recent studies still show significant analytical discrepancies in the analysis of animal tissues and fluids, despite the development of instrumental techniques such as TIMS, ICP-MS, ICP-ES, ICAP, SIMS, NA-MS, PGAA, NRA, and so forth, which have demonstrated detection limits approaching or exceeding (microg B/kg concentrations. Since boric acid is both volatile and ubiquitous in nature, the chemical and physical pathways for B contamination and its loss are manifold, especially during sample preparation. An added obstacle is the inadequacy of biological reference materials certified for B below mg B/kg. With an emphasis toward sample preparation and ICP-MS analysis, examples are provided in this article to help the analyst avoid common problems associated with the analysis of B from biological sources. Topics that are discussed include contamination from Teflon vessels during microwave digestion, losses owing to freeze-drying, B isotopic variations, standards preparation, reagent backgrounds, and instrumental interferences.

Determining human dietary requirements for boron.

A dietary requirement is defined as the lowest continuing intake of a nutrient that for a specified indicator of adequacy, will maintain a defined level of nutriture in an individual. An essential dietary component is one that the body cannot synthesize in sufficient quantities to maintain health. Recommended dietary allowances (RDAs) are based on estimates of the dietary requirements, and are designed to prevent deficiency diseases and promote health through an adequate diet. In 1996, the Food and Nutrition Board (FNB) began a revision process of the RDAs using as criteria specific indicators of adequacy and functional end points for reducing the risk of chronic disease. Boron (B) is a dietary component, and evidence from animal studies indicates that it is a dietary essential; it cannot be synthesized in tissues, and organisms exposed to very low levels of B show developmental defects. In humans, there is evidence of homeostatic regulation of B and an interrelationship with bone metabolism. To understand better the relationship between dietary B and B homeostasis, we measured the dietary B intake and urinary B losses in seven male participants of a controlled metabolic study of Zn homeostasis. Average dietary B intake for the repeated menu days, days 1, 2, and 3, was 4.56, 1.87, and 4.75 mg/d, respectively. Urinary B excretion during the 42-d collection period averaged 3.20 +/- 0.41 mg/d. When dietary B was low, urinary B loss (2.92 mg/d) was significantly lower than when B intake was higher (3.15 and 3.54 mg/d). Our study showed that urinary B excretion changes rapidly with changes in B intake, indicating that the kidney is the site of homeostatic regulation. To enable establishment of a dietary requirement for B in the future, further research of homeostatic regulation and functional markers of B metabolism need to be performed, followed by epidemiological studies to identify health conditions associated with inadequate dietary B.

Serum boron concentration from inhabitants of an urban area in Japan. Reference value and interval for the health screening of boron exposure.

Boron (B) levels were determined in the serum of 980 healthy inhabitants living in an urban area of Japan by means of inductively coupled plasma emission spectrometry (ICPES). The results showed a log-normal distribution of serum B for both sexes, although there are age-related differences. In male subjects, serum B increases rapidly up to 49 yr of age, reaching a plateau between ages 50 and 69 yr old, followed by a gradual increase up to 70 yr or older. Female subjects exhibit a gradual increase up to the age of 70 yr old. The reference value for male and female subjects was 79.8 micrograms/L and 67.9 micrograms/L, and the reference interval was 33.3-191.2 micrograms/L and 29.5-154.9 micrograms/L, respectively. The obtained reference value and interval of the nonexposed group may be useful for health screening for B exposure, either for people living in regions with high levels of B in the environment, or for workers who are exposed to this element.

Teatment planning figures of merit in thermal and epithermal boron neutron capture therapy of brain tumours.

The boron neutron capture therapy (BNCT) figures of merit of advantage depth, therapeutic depth, modified advantage depth and maximum therapeutic depth have been studied as functions of 10B tumour to blood ratios and absolute levels. These relationships were examined using the Monte Carlo neutron photon transport code, MCNP, with an ideal 18.4 cm diameter neutron beam incident laterally upon all ellipsoidal neutron photon brain-equivalent model. Mono-energetic beams of 0.025 eV (thermal) and 35 eV (epithermal) were simulated. Increasing the tumour to blood 10B ratio predictably increases all figures of merit. concentration was also shown to have a strong bearing on the figures of merit when low levels were present in the system. This is the result of a non-10B dependent background dose. At higher levels however, the concentration of 10B has a diminishing influence. For boron sulphydryl (BSH), little advantage is gained by extending the blood 10B level beyond 30 ppm, whilst for D,L,-p-boronophenylalanine (BPA) this limit is 10 ppm. To achieve a therapeutic depth of 6 cm (brain mid-line from brain surface) using the thermal beam, a tumour to blood ratio of 25 with 10 ppm 10B in the blood is required for BPA. Similarly, a tumour to blood ratio of 8.5 with 30 ppm blood 10B is required for the maximum therapeutic depth of BSH to reach the brain mid-line. These requirements are five times above current values for these compounds in humans. Applying the epithermal beam under identical conditions, the therapeutic depth reaches the brain mid-line with a tumour to blood 10B ratio of only 5.7 for BPA. For BSH, the maximum therapeutic depth reaches the brain mid-line with a tumour to blood ratio of only 1.9 with 30 ppm in the blood. Human data for these compounds are very close to these requirements.