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Absorption of boron after mouthwash treatment with Bocosept.

Healthy volunteers and patients with gingivitis were treated locally with the boron-containing bacteriostatic agent, Bocosept. Blood levels and urinary excretion of boron were examined by a spectrophotometric method. Blood concentrations after a single mouthwash with Bocosept slightly exceeded those after intake of 200 g raisins or a bottle of red wine. The blood levels during a one-week course of treatment showed a low rate of boron accumulation. The highest concentration was about 0.3 microgram B/ml, a level which does not seem to involve any risk of boron poisoning. The small amount taken up after mouthwash treatment with Bocosept does not appear to represent absorption by the oral mucosa. It seems more likely that the uptake of boron takes place in the intestine after ingestion of residual amounts from the mouth.

Absorption↗

Acute toxicity of boron, molybdenum, and selenium to fry of chinook salmon and coho salmon.

The acute toxicities of boron, molybdenum, and various forms of selenium, individually and in environmentally relevant mixtures, to swim-up and advanced fry of chinook salmon (Oncorhynchus tshawytscha) and coho salmon (O. kisutch) were determined in site-specific fresh and brackish waters. Boron and molybdenum were relatively non-toxic (96-hr LC50s greater than 100 mg/L) to both life stages of both species. Selenite was significantly more toxic than selenate to both species. Swim-up fry tested in fresh water were significantly more sensitive than advanced fry in brackish water to selenate and selenite. No mortalities occurred in any concentrations tested of seleno-DL-methionine; however, in the highest concentration (21.6 mg Se/L), at least 50% of the fish showed pronounced surfacing behavior. Coho salmon were more sensitive than chinook salmon to both selenate and selenite at either life stage; only the swim-up fry of coho salmon were more sensitive than chinook salmon to boron. In additional tests with swim-up chinook salmon, differences in the characteristics of the dilution water did not significantly modify the relative toxicities of boron, selenate, and selenite. In binary mixture studies, the joint acute toxic action of selenate and selenite, combined in various ratios, was additive to both species. Based on a comparison of the individual acute values for chinook salmon to the expected environmental concentrations, the margin of safety for boron was only 56 in fresh and 46 in brackish water. The margins of safety for selenate and selenite exceeded 275 in both fresh and brackish waters. However, the margin of safety for both selenate and selenite in the mixture test was 145 in fresh water and 220 in brackish water.

Animals↗

Boron tolerable intake: re-evaluation of toxicokinetics for data-derived uncertainty factors.

Boron, which is ubiquitous in the environment, causes developmental and reproductive effects in experimental animals. This observation has led to efforts to establish a Tolerable Intake value for boron. Although risk assessors agree on the use of fetal weight decreases observed in rats as an appropriate critical effect, consensus on the adequacy of toxicokinetic data as a basis for replacement of default uncertainty factors remains to be reached. A critical analysis of the existing data on boron toxicokinetics was conducted to clarify the appropriateness of replacing default uncertainty factors (10-fold for interspecies differences and 10-fold for intraspecies differences) with data-derived values. The default uncertainty factor for variability in response from animals to humans of 10-fold (default values of 4-fold for kinetics and 2.5-fold for dynamics) was recommended, since clearance of boron is 3- to 4-fold higher in rats than in humans and data on dynamic differences--in order to modify the default value--are unavailable. A data-derived adjustment of 6-fold (1.8 for kinetics and 3.1 for dynamics) rather than the default uncertainty factor of 10-fold was considered appropriate for intrahuman variability, based on variability in glomerular filtration rate during pregnancy in humans and the lack of available data on dynamic differences. Additional studies to investigate the toxicokinetics of boron in rats would be useful to provide a stronger basis for replacement of default uncertainty factors for interspecies variation.

Animals↗

The effect of in ovo boron supplementation on bone mineralization of the vitamin D-deficient chicken embryo.

It has been hypothesized that boron (B) is an essential element for animals, but its action will vary greatly depending on the nutriture of the organism. One of the nutrients implicated as having an interaction with boron is cholecalciferol (Vit D3). This study was carried out to determine if such an interaction exists. The study was conducted utilizing vitamin D-deficient chicken embryos that were injected through the shell at 8 d of embryogenesis with carrier (NaCl and/or acetone), B (0.5 mg), B + Vit D3 (0.5 mg and 0.3 microgram, respectively), or Vit D3 (0.3 or 1.5 micrograms). The in ovo concomitant administration of boron and vitamin D enhanced (p less than 0.05) the hatchability of the vitamin D-deficient embryos. Furthermore, boron and/or vitamin D3 increased (p less than 0.05) the percent of bone ash and decreased (p less than 0.05) the exaggerated height of the proliferative zone of the epiphyseal growth plate normally observed in vitamin D deficiency, suggesting a more rapid bone formation. The results provide further evidence supporting the hypothesis that boron plays a role in bone mineralization through an interaction with vitamin D.

Analysis of Variance↗

Effect of boron on vitamin D deficient rats.

The effects of different levels of dietary boron were determined in vitamin D deficient rats. Vitamin D deficient diets containing either 0.158 ppm or 2.72 ppm of boron were fed to rats for 11 w, and calcium, magnesium, and phosphorus apparent absorption and balance were measured in the twelfth week. Higher apparent absorption and balance values for calcium and phosphorus were observed in the rats with higher dietary boron, but very few differences were seen in body wt, organ wt, and bone parameters. Balance measurements represented the present status of the rats after 12 w on the diets, but other measurements represented an accumulation over the lifetime of the rat, including a suckling period with ample vitamin D and boron. The data demonstrated that when rats are vitamin D deficient, as indicated by hypocalcemia, the level of boron in the diet affects mineral balance.

Animals↗

Inhibition of human milk bile-salt-dependent lipase by boronic acids. Implication to the bile salts activator effect.

The bile-salt-dependent lipase from human milk, which catalyzes the hydrolysis of the water-soluble substrate 4-nitrophenyl acetate and the water-insoluble substrate tributyrin, is competitively inhibited by phenyl boronic acid. This inhibitor does not interfere with the interaction of lipase either with the siliconized glass beads/water interface or with the activator bile-salt binding site. The boronic acid binds near or at the active site serine, since modification of this residue by diisopropylphosphofluoridate (DFP) was prevented by phenyl boronic acid. Phenyl boronic acid binds 15-fold as tightly to bile-salt-dependent lipase as does 4-nitrophenyl acetate. Therefore, phenyl boronic acid bears analogy to a substrate rather than to a tetrahedral intermediate analog. Bile salts such as sodium taurocholate which are non-essential activators for the milk lipase activity on water-soluble substrates decrease the Km as well as the enzyme inhibitor dissociation constant (Ki). They have a slight effect on kcat. These results are interpreted in terms of an increase of the stability of the enzyme-substrate tetrahedral intermediate and in general of any transition states for the formation and for the decomposition of these intermediates upon the enzyme bile salts interaction.

Adsorption↗

15 beta-hydroxysteroids (Part III). Steroids of the human perinatal period: the synthesis of 3 beta, 15 beta, 17 alpha-trihydroxy-5-pregnen-20-one. Application of n-butyl boronic acid protection of a 17,20-glycol.

We report the synthesis of 3 beta,15 beta,17 alpha-trihydroxy-5-pregnen-20- one (1) from 3 beta,15 beta-dihydroxy-5,16-pregnadien-20-one (11) in 7 steps using boronate derivatives as a means of protecting the 17,20-glycol side-chain of steroid intermediates. 16 alpha,17 alpha-Epoxy-3 beta,15 beta-dihydroxy-5- pregnen-20-one (12), an intermediate in the synthesis was prepared by epoxidation of 11 using a mixture of sodium hydroxide and hydrogen peroxide. Reduction of 12 with lithium aluminium hydride gave the two isomers of 5-pregnene-3 beta, 15 beta,17 alpha,20 (S+R)-tetrol (13a and 13b) which on subsequent reaction with n-butyl boronic acid gave 5-pregnene-3 beta,15 beta,17 alpha, 20(S+R)-tetrol 17 alpha,20-butyl boronate (15a and 15b). Acetylation with acetic anhydride and pyridine yielded 3 beta,15 beta-diacetoxy-5-pregnene-17 alpha,20(S+R)-diol 17 alpha,20(S+R)-butyl boronate (15c and 15d). Oxidative cleavage of the boronic ester using sodium hydroxide and hydrogen peroxide gave 3 beta,15 beta-diacetoxy-5-pregnene-17 alpha,20(S+R)-diol (13c and 13d). After isolation of these latter two products, dibromide protection of the C-5,6 olefin of 13d and oxidation with N-bromosuccinimide gave 3 beta,15 beta-diacetoxy-17 alpha-hydroxy-5-pregnen-20-one (16) which on deacetylation gave in good yield (35%) the desired product 3 beta,15 beta,17 alpha-trihydroxy-5-pregnen-20-one (1) in an overall yield of 24% from 11.

17-alpha-Hydroxypregnenolone↗

Boron neutron capture enhancement of 252Cf brachytherapy.

Dosimetric and radiobiological studies were undertaken to investigate the potential enhancement in dose, dose distribution and cell killing effectiveness of 252Cf brachytherapy achievable when boron-10 enriched compounds are incorporated into simulated 252Cf brain implants. Thermal neutron distributions in a human head phantom containing a 252Cf source were measured by gold foil activation and calculated using a 1-dimensional transport code. This information was then used to modify measured event size distributions for 252Cf neutrons to determine the corresponding increase in dose and dose equivalent throughout the phantom. The addition of subtoxic levels of boron-10 to a typical 252Cf implant was found to significantly enhance both the absorbed dose and the high LET event frequency at distances of 3 to 5 cm from individual sources. Some unexpected geometric considerations are discussed. Reduced survival of cultured Chinese hamster cells correlated with the predicted increase in absorbed dose from the capture events with a concentration of about 60 micrograms 10B per ml in the culture medium. It was found that boron increased alpha (the "single-hit" parameter of the linear quadratic survival model) by 32% and decreased beta (the "double-hit" parameter) by 8%. The alpha/beta ratio increased to 4.34 Gy in the presence of boron, from 3.03 Gy in its absence. This translated to an 8% reduction in californium dose needed to effect 10% cell survival. It is concluded that there is a sufficiently high thermal neutron fluence present during californium brachytherapy for boron neutron capture dose augmentation to be feasible.

Animals↗

Boron ameliorates fulminant hepatic failure by counteracting the changes associated with the oxidative stress.

Boron has well-defined biological effects and may be of therapeutic benefit. In the current paper, the effect of boron in the form of borax was tested in experimental animal model of fulminant hepatic failure (FHF). The syndrome was induced in female Wistar rats by three consecutive daily intraperitoneal injections of thioacetamide (400 mg/kg). In the treatment groups, rats received borax (4.0 mg/kg) orally for three consecutive days followed by thioacetamide. The group administered with thioacetamide plus vehicle, and the borax alone treated rats served as controls. In all groups, rats were terminated 4 h after administering the last dose of thioacetamide, and the tissue/serum was used to measure hepatic levels of thiobarbituric acid reactive substances, reduced glutathione, and various enzymes associated with oxidative stress including peroxide metabolizing enzymes and xanthine oxidase. In thioacetamide treated group, many fold increase in the activity level of serum marker enzymes suggesting FHF was observed that could be brought down significantly in rats receiving boron. Modulation and a correlation in the activity level of oxidant generating enzyme and lipid peroxidation as well as hepatic glutathione level was also observed in rats receiving thioacetamide. In the group receiving boron followed by thioacetamide, these changes could be minimized moderately. The activity level of the peroxide metabolizing enzymes and the tripeptide glutathione, which decreased following thioacetamide treatment were moderately elevated in the group receiving boron followed by thioacetamide. The data clearly shows that borax partly normalizes the liver and offsets the deleterious effects observed in FHF by modulating the oxidative stress parameters.

Animals↗

Evaluation of boron removal from water by hydrotalcite-like compounds.

Layered double hydroxides (LDHs) or hydrotalcite (HT)-like compounds with different kinds of metal ions (Mg-Al and Mg-Fe) in the brucite-like sheets were prepared and their adsorption properties were studied in the boron removal from aqueous solution under laboratory conditions. The hydrotalcites were synthesized by the coprecipitation method and were characterized by chemical analyses, X-ray diffraction (XRD), Fourier Transform infrared spectroscopy (FTIR) and specific surface area measurements (BET). The affinity of these materials with a mixture of B(OH)(3) and B(OH)(4)(-) was studied as a function of contact time, initial pH of the solutions, HT quantity and B concentration (adsorption isotherms). It was found that 120 min is enough time for the equilibrium state to be reached in boron adsorption. Boron removal was independent of the initial pH of the solutions because of the high buffering capacity of the LDHs. On the other hand, the adsorption capacity increases with increasing the adsorbent quantity. The adsorption isotherms, described by the Langmuir model, are of L-type, suggesting that B(OH)(4)(-) is adsorbed preferentially on HT-like materials. Besides, Mg-Al hydrotalcites showed higher adsorption capacity than Mg-Fe. We proposed that in Mg-Al hydrotalcites, the boron removal occurs by both adsorption on external surface and ion exchange, whereas for Mg-Fe it occurs only by surface adsorption. After treatment of a solution containing 5.2 mgBl(-1) with Mg-Al hydrotalcites the final boron concentration reached the recommended limit by WHO for drinking water (0.5 mgl(-1)).

Adsorption↗

An anion-exchange chromatographic study on boron isotopic fractionation at 2 MPa at 293 K.

To study boron isotopic fractionation at high pressure, column chromatography operated in the breakthrough manner was performed at 2.0 MPa at 25.0 degrees C. The fractionation factor (S) between boron adsorbed onto strongly basic anion-exchange resin and boron in solution was obtained as 1.013, which was smaller than the values at 0.1 MPa (atmospheric pressure) found in literature. The pressure dependence of S was discussed based on the polymerization of boron in the solution and resin phases and on the occurrence of the pressure dependent isotope effect relating to the molar volume changes of boron species upon isotope substitution.

Anion Exchange Resins↗

Manipulating the fragmentation patterns of phosphopeptides via gas-phase boron derivatization: determining phosphorylation sites in peptides with multiple serines.

Trivalent boron species readily react with protonated phosphopeptides to give addition products with the loss of boron ligands. In the present study, trimethoxyborane (TMB), diisopropoxymethylborane (DIPM), and diethylmethoxyborane (DEMB) were allowed to react with four phosphopeptides, VsSF, LSsF, LsGASA, and VSGAsA (lower-case s indicates phosphoserine). Each of the phosphopeptides contains one serine that is phosphorylated and one that is not. Under collision-activated dissociation (CAD) conditions, the boron-derivatized peptides give fragmentation patterns that differ significantly from that of the protonated phosphopeptide. The patterns vary, depending on the number of labile (i.e., alkoxy) ligands on the boron. In general, boron derivatization increases the yield of phosphate-containing sequence ions, but dramatic effects are only seen with certain reagent/peptide combinations. However, the suite of reagents provides a means of altering and increasing the information content of phosphopeptide CAD spectra.

Algorithms↗

Removal of boron from aqueous solution by adsorption on Al2O3 based materials using full factorial design.

This paper aims the adsorption of boron from aqueous solution onto Siral 30 and Pural using 2(3) full factorial design. The effect of individual variables and their interactional effects for boron adsorption were also determined. From the statistical analysis, it is inferred that as pH and temperature increased boron adsorption from aqueous solution decreased. Siral 30 was found to be more efficient adsorbent than Pural. The unimportant factor affecting boron adsorption from aqueous solution was also verified by using Fisher adequacy test. At the 90% confidence level, the type of adsorbent, temperature and type of adsorbent-temperature interaction was effective on boron adsorption from aqueous solution. The experimental results were fitted to the Langmuir, Freundlich and Dubinin-Radushkevich (DR) equations to find out adsorption capacities. In most cases, the results indicate that Freundlich and DR equations are well described with the sorption data. The adsorption capacity values of Siral 30 calculated from Freundlich and DR equation was greater than that of Pural. The thermodynamic parameters were also estimated and the adsorption process was not spontaneous nature.

Adsorption↗

Application of iron-rich natural clays in Camlica, Turkey for boron sorption from water and its determination by fluorimetric-azomethine-H method.

In this study, iron-rich natural Camlica Bentonites, CB1 and CB2, were used for the sorption of boron in water samples. Boron was determined by newly progressed fluorimetric azomethine-H method. The optimum conditions found using factorial designs are pH 10, 45 degrees C, 0.250 g of clay and 20 mL of sample volume. It was found that 180 min is enough time for the equilibrium state to be reached in boron adsorption. At these conditions, boron sorption percentage was 80% for CB1 and 30% for CB2. The adsorption isotherms are well described by linear Freundlich model. Various geothermal waters in our country were also studied for boron sorption.

Adsorption↗

Precipitation recovery of boron from wastewater by hydrothermal mineralization.

It is well known that boric acid exhibits various toxic effects on plant, animal and human beings even at very low concentrations. Thus, the development of boron-removal technique from wastewater has been intensively investigated. In this study, a new hydrothermal treatment technique was developed to recover boron as recyclable precipitate Ca(2)B(2)O(5).H(2)O from aqueous solutions. As a result, it was found that the hydrothermal treatment using calcium hydroxide as a mineralizer converted boron in the aqueous media effectively into calcium borate, Ca(2)B(2)O(5).H(2)O. In the optimal hydrothermal condition, more than 99% of boron was collected from the synthetic wastewater of 500 ppm. Thus, the present hydrothermal treatment in the presence of calcium hydroxide is recommended as one of the effective techniques to recover boron from aqueous media.

Borates↗

Determination of the aquatic PNEC0.05 for boron.

Several weight of the evidence approaches for the effects assessment of boron to aquatic organisms have been conducted. The focal point for all of these assessments is the appropriate interpretation of the LC1 for rainbow trout (Oncorhynchus mykiss) from W.J. Birge, J.A. Black, Report No. EPA5601176408. Environmental Protection Agency, Office of Toxic Substances, Washington, DC, 1977, as the LC1 from their studies provided the lowest chronic toxicity values for boron. Other studies by these investigators (W.J. Birge, J.A. Black, Completion Report prepared for the Procter & Gamble Company, Cincinnati, USA, 1981; W.J. Birge, J.A. Black, A.G. Westermann, T.M. Short, S.B. Taylor, M.C. Parekh. Completion Report prepared for the Procter & Gamble Company, Cincinnati, USA, 1984; J.A. Black, J.B. Barnum, W.J. Birge, Chemosphere 26 (1993) 1383-1413) further indicate this species to be particularly sensitive to boron. While weight of the evidence approaches have been necessary for diverse risk assessment needs, they each suffer from potential bias via professional judgment. In order to allay these issues and to update the effects assessment for boron, a probabilistic approach was used. Raw data from the Birge and Black studies were reanalyzed to generate chronic values representative of the adverse effects threshold (e.g., LC10) for several species. A comprehensive list of chronic data from these studies and other studies were combined into a cumulative probability term, allowing for the determination of the fifth percentile protection value, or PNEC0.05. The PNEC0.05 for boron was determined to be at least 1.3 mg B/l.

Animals↗

Boron levels in man: preliminary evidence of genetic regulation and some implications for human biology.

Boron is a ubiquitous constituent of man's external environment. Levels of the element in human blood reflect both acute and chronic exposure, usually as dietary intake (food and drinking water). There is an absolute requirement for boron in vascular plants but evidence for biological essentiality in animals (including man) is limited. A high body burden of the element may be harmful, especially to young animals (including human neonates). Information on boron deficiency is scanty. It has been proposed that boron contributes to living systems by acting indirectly as a proton donor and that it exerts a particular influence on cell membrane structure and function. The present study examines the variation in blood levels within and between human sibships and provides some support for the possibility that boron metabolism is subject to genetic regulation.

Adult↗

Boron neutron capture therapy of brain tumors: enhanced survival following intracarotid injection of sodium borocaptate with or without blood-brain barrier disruption.

PURPOSE: Sodium borocaptate (Na2B12H11SH or BSH) has been used clinically for boron neutron capture therapy (BNCT) of patients with primary brain tumors. The purpose of the present study was to determine if tumor uptake of BSH and efficacy of BNCT could be enhanced in F98 glioma-bearing rats by intracarotid (i.c.) injection of the compound with or without blood-brain barrier disruption (BBB-D). METHODS AND MATERIALS: For biodistribution studies 100,000 F98 glioma cells were implanted stereotactically into the brains of Fischer rats, and 12 days later BBB-D was carried out by i.c. infusion of 25% mannitol, followed immediately thereafter by i.c. injection of BSH (30 mg B/kg body weight). Animals were killed 1, 2.5, and 5 h later, and their brains were removed for boron determination. For BNCT experiments, which were initiated 14 days after intracerebral implantation of 1000 F98 cells, BSH (30 mg B/kg b.wt. was administered intravenously (i.v.) without BBB-D, or i.c. with or without BBB-D. The animals were irradiated 2.5 h later with a collimated beam of thermal neutrons at the Brookhaven National Laboratory Medical Research Reactor. RESULTS: The mean tumor boron concentration after i.c. injection with BBB-D was 48.6 +/- 17.2 microg/g at 2.5 h compared with 30.8 +/- 12.2 microg/g after i.c. injection without BBB-D and 12.9 +/- 4.2 microg/g after i.v. injection. The best composite tumor to normal tissue ratios were observed at 2.5 h after BBB-D, at which time the tumor:blood (T:B1) ratio was 5.0, and the tumor: brain (T:Br) ratio was 12.3, compared to 1.1 and 4.6, respectively, in i.v. injected rats. The mean survival time for untreated control rats was 24 +/- 3 days, 29 +/- 4 days for irradiated controls, 33 +/- 6 days for those receiving i.v. injection of BSH, 40 +/- 8 days for rats receiving i.c. BSH without BBB-D, and 52 +/- 13 days for BBB-D followed by BNCT (p = 0.003 vs. i.v. injected BSH). CONCLUSIONS: Intracarotid administration of BSH with or without BBB-D significantly increased tumor uptake of BSH and enhanced survival of F98 glioma-bearing rats following BNCT. BBB-D may be a useful way to enhance the delivery of both low and high molecular weight boron compounds to brain tumors. Further studies are in progress to assess this approach with other boron delivery agents.

Animals↗