Global analysis of boron-induced ribosome stalling reveals its effects on translation termination and unique regulation by AUG-stops in Arabidopsis shoots.

We previously reported that ribosome stalling at AUG-stop sequences in the 5'-untranslated region plays a critical role in regulating the expression of Arabidopsis thaliana NIP5;1, which encodes a boron uptake transporter, in response to boron conditions in media. This ribosome stalling is triggered specifically by boric acid, but the mechanisms are unknown. Although upstream open reading frames (uORFs) are known in many cases to regulate translation through peptides encoded by the uORF, AUG-stop stalling does not involve any peptide synthesis. The unique feature of AUG-stops - that termination follows immediately after initiation - suggests a possible effect of boron on the translational process itself. However, the generality of AUG-stop-mediated translational regulation and the effect of boron on translation at the genome scale are not clear. Here, we conducted a ribosome profiling analysis to reveal the genome-wide regulation of translation in response to boron conditions in A. thaliana shoots. We identified hundreds of translationally regulated genes that function in various biological processes. Under high-boron conditions, transcripts with reduced translation efficiency were rich in uORFs, highlighting the importance of uORF-mediated translational regulation. We found 673 uORFs that had more frequent ribosome association. Moreover, transcripts that were translationally downregulated under high-boron conditions were rich in minimum uORFs (AUG-stops), suggesting that AUG-stops play a global role in the boron response. Metagene analysis revealed that boron increased the ribosome occupancy of stop codons, indicating that this element is involved in global translational termination processes.

Birth weights of newborns and pregnancy outcomes of environmentally boron-exposed females in Turkey.

Boric acid and sodium borates are currently classified as being toxic to reproduction under "Category 1B" with the hazard statement of "H360 FD" in the European CLP regulation. This has prompted studies on boron-mediated reprotoxic effects in male workers in boron mining areas and boric acid production plants. By contrast, studies on boron-mediated developmental effects in females are scarce. The present study was designed to fill this gap. Hundred and ninety nine females residing in Bandirma and Bigadic participated in this study investigating pregnancy outcomes. The participants constituted a study group covering blood boron from low (< 100 ng B/g blood, n = 143) to high (> 150 ng B/g blood, n = 27) concentrations. The mean blood boron concentration and the mean estimated daily boron exposure of the high exposure group was 274.58 (151.81-975.66) ng B/g blood and 24.67 (10.47-57.86) mg B/day, respectively. In spite of the high level of daily boron exposure, boron-mediated adverse effects on induced abortion, spontaneous abortion (miscarriage), stillbirth, infant death, neonatal death, early neonatal death, preterm birth, congenital anomalies, sex ratio and birth weight of newborns were not observed.

Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model.

The application of boron neutron capture therapy (BNCT) mediated by liposomes containing (10)B-enriched polyhedral borane and carborane derivatives for the treatment of head and neck cancer in the hamster cheek pouch oral cancer model is presented. These liposomes are composed of an equimolar ratio of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine, incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] (MAC) in the bilayer membrane while encapsulating the hydrophilic species Na3[ae-B20H17NH3] (TAC) in the aqueous core. Unilamellar liposomes with a mean diameter of 83 nm were administered i.v. in hamsters. After 48 h, the boron concentration in tumors was 67 ± 16 ppm whereas the precancerous tissue contained 11 ± 6 ppm, and the tumor/normal pouch tissue boron concentration ratio was 10:1. Neutron irradiation giving a 5-Gy dose to precancerous tissue (corresponding to 21 Gy in tumor) resulted in an overall tumor response (OR) of 70% after a 4-wk posttreatment period. In contrast, the beam-only protocol gave an OR rate of only 28%. Once-repeated BNCT treatment with readministration of liposomes at an interval of 4, 6, or 8 wk resulted in OR rates of 70-88%, of which the complete response ranged from 37% to 52%. Because of the good therapeutic outcome, it was possible to extend the follow-up of BNCT treatment groups to 16 wk after the first treatment. No radiotoxicity to normal tissue was observed. A salient advantage of these liposomes was that only mild mucositis was observed in dose-limiting precancerous tissue with a sustained tumor response of 70-88%.

The efficacy and safety of tavaborole, a novel, boron-based pharmaceutical agent: phase 2 studies conducted for the topical treatment of toenail onychomycosis.

OBJECTIVE: To assess the potential efficacy, safety, and optimal dosing concentration of tavaborole, a novel, boron-based pharmaceutical agent with broad-spectrum antifungal activity, for the treatment of onychomycosis of the toenail due to dermatophytes. METHODS: One double-blind, randomized, vehicle-controlled study (study 1) and two open-label studies (studies 2 and 3) examined the efficacy, safety, and optimal dosing concentration of tavaborole topical solution applied once daily or three times weekly for 180 days at concentrations of 1.0%, 2.5%, 5.0%, or 7.5%. Patient cohort 3 of study 2 received open-label tavaborole 5.0% once daily for 360 days. All three studies assessed day 180 treatment success, defined as complete or partial clinical evidence of clear nail growth plus negative fungal culture. RESULTS: A total of 336 patients were included in the intent-to-treat (ITT) or modified ITT populations and efficacy analyses across the 3 studies. In study 1, treatment success rates at day 180 were higher with tavaborole 2.5%, 5.0%, and 7.5% vs vehicle (27%, 26%, and 32% vs 14%, respectively; slope P=0.030). In cohort 3 of study 2, 7% of patients achieved treatment success with tavaborole 5.0% at day 360. Negative culture rates at day 180 in study 1 were numerically higher for tavaborole 2.5%, 5.0%, and 7.5% vs vehicle (slope P=0.046). Application-site reactions of general irritation, erythema, scaling, and stinging/burning were most common with tavaborole 7.5%, were generally mild to moderate, and resolved with treatment discontinuation and/or a reduction in dosing frequency. No systemic safety concerns were observed. CONCLUSION: Tavaborole solution demonstrated favorable efficacy and safety in phase 2 clinical studies. Based on these findings, tavaborole topical solution, 5% was further investigated in larger, more definitive phase 3 studies. Results from these completed phase 3 studies will provide additional evidence regarding the safety and efficacy of tavaborole in the treatment of toenail onychomycosis.

Effects of Boron and NaCl on Antioxidant Defence Mechanisms in Duckweeds (Spirodela polyrhiza L.).

<b>Background and Objective:</b> Boron is one of the principal elements required for plant's growth but extreme amounts of boron are toxic to humans, animals and plants. This study aimed to utilized growth rates, dry biomass and antioxidant enzyme activities to evaluate the potential of <i>Spirodela polyrhiza</i> L., in which <i>S. polyrhiza</i> produced for 120 hrs in water containing control, 10, 20, 40 and 80 mg L¹ of Boron and sodium chloride (NaCl) concentrations changing from 0-50 mM. <b>Materials and Methods:</b> In this study, we have done with <i>S. polyrhiza</i>, Boron and NaCl applications were continued for 120 hrs. After 120 hrs, the plants were harvested, cleaned with pure water, frozen at fluid nitrogen and stored at -80°C until further usage for enzymes activity. To determine the amount of Boron in <i>S. polyrhiza</i>, the samples were dried at 70 and then measured with Thermo ICP-MS. <b>Results:</b> The results indicated that the Boron accumulation capacity of <i>S. polyrhiza</i> diminished with accelerating salinity. <i>Spirodela polyrhiza</i> may have utilized various mechanisms to collecting Boron in high and low salt concentrations. As a conclusion of the study, it was stated that the growth rate of <i>S. polyrhiza</i> and total chlorophyll synthesis were considerably obstructed when NaCl amounts reached 50 mM. <b>Conclusion:</b> Our results indicate that CAT, APX and SOD can serve as substantial biomarkers in Boron-rich habitats. This <i>S. polyrhiza</i> is a very beneficial exemplary plant for phytoremediation advancement of contaminated wastewater with low Boron content.

Evaluation of chronically implanted subdural boron doped diamond/CNT recording electrodes in miniature swine brain.

When implantable recording devices for brain or neural electrical activity are designed, the number of available materials for electrodes is quite limited. The material must be biocompatible with respect to ISO10993, its electrochemical properties must remain stable and the response of cells or tissues can be mitigated, especially on the glial scar. This involves electrode characterization pre- implantation and impedance spectroscopy during chronic implantation, in order to evaluate both electrode properties and performance. This study was aimed at a comparison of the long-term behavior of a nanostructured boron-doped diamond (BDD) with a nanostructured Platinum Iridium (PtIr) electrode. Firstly, a batch of cortical grids with bare and modified contacts (2 mm in diameter) was engineered for implantation. Secondly a miniature swine model was developed. This study highlighted the predominant role of electrode surface roughness on the quality of recordings. Rough PtIr contacts and BDD coated ones showed comparable behavior after three-month implantation with a slight increase of the modulus of the impedance and a tissue capsule. Nevertheless, immunohistochemistry analysis did not exhibit either a toxic or irritation reaction. With regard to biocompatibility, promising long term results are shown for both materials.

Environmental boron exposure does not induce DNA damage in lymphocytes and buccal cells of females: DNA damage in lymphocytes and buccal cells of boron exposed females.

Boron (B) compounds are essential for plants and animals and beneficial for humans in nutritional amounts. I animals and humans increasing evidence have shown beneficial effects on B compounds on nutrition and on antioxidant status. The genotoxic effects of environmental B exposure in women living in boron-rich and boron-poor areas was examined in this study. For this purpose, the DNA damage in the lymphocytes and buccal cells of females were assessed by Comet and micronucleus (MN) assays respectively. No significant difference was observed in the DNA damage of the lymphocytes of B exposed groups of female volunteers in Comet assay. Even buccal micronucleus (MN) frequency observed in the high exposure group was significantly lower than the low exposure group (p < 0.05). The results of this study came to the same conclusions of the previous studies that boron does not induce DNA damage even under extreme exposure conditions.

Acute exposure to boron in Nile tilapia (Oreochromis niloticus): Median-lethal concentration (LC50), blood parameters, DNA fragmentation of blood and sperm cells.

Recently, Boron (B) contamination of aquatic ecosystem has received considerable critical attention due to its toxic effects at high concentrations on plants as well as animals. Previous studies on toxic effects of B have not dealt with DNA damages in blood and sperm cells of Nile tilapia (Oreochromis niloticus), together with blood parameters. This study consisted of two successive experiments purposes to determine these findings, including the median-lethal concentration (LC50) of B for Nile tilapia. In the first one, at 96 h, LC50 of B for Nile tilapia was 141.42 mg L-1 B. In the second one, Nile tilapia were treated with five elevated B concentrations (1, 5, 25, 50 and 100 mg L-1 B) and hematological, serum biochemical parameters, and DNA damages of Nile tilapia in these treatments were determined comparing with the control after 14 days of exposure. Hematological parameters (red blood cell count, hematocrit, and hemoglobin) were similar to each other in all groups while serum biochemical parameters (glucose, total protein, cholesterol, alkaline phosphatase, glutamic oxaloacetic transaminase, and glutamic pyruvic transaminase) in B treatments, especially in 50 and 100 mg L-1 B groups, were found significantly higher (P < 0.05). DNA fragmentation was detected in all blood cells in ≥25 mg L-1 B treatments, while all sperm cells in 100 mg L-1 B treatments. These results demonstrated the harmful effects of B at high concentration (50 and 100 mg L-1 B) on the DNA integrity of blood and sperm cells, and also the serum biochemical parameters.

Boron - A potential goiterogen?

The iodine deficiency disorders (IDD) include a variety of disturbances such as decreased fertility, increased perinatal and infant mortality, impaired physical and intellectual development, mental retardation, cretinism, hypothyroidism, and endemic goiter (EG). The occurrence of the latter is determined by interplay between genetic and environmental factors. The major environmental factor is iodine status that is required for normal thyroid hormone synthesis. However, other factors like intake of micronutrients and goiterogens also have a significant impact. Essential and toxic trace elements both play a significant role in thyroid physiology. We hypothesize that in terms of overexposure boron may serve as a potential goiterogen. In particular, it is proposed that boron overload may impair thyroid physiology ultimately leading to goiter formation. Certain studies provide evidential support of the hypothesis. In particular, it has been demonstrated that serum and urinary B levels are characterized by a negative association with thyroid hormone levels in exposed subjects. Single indications on the potential efficiency of B in hypothyroidism also exist. Moreover, the levels of B were found to be interrelated with thyroid volume in children environmentally exposed to boron. Experimental studies also demonstrated a significant impact of boron on thyroid structure and hormone levels. Finally, the high rate of B cumulation in thyroid may also indicate that thyroid is the target for B activity. Chemical properties of iodine and boron also provide a background for certain competition. However, it is questionable whether these interactions may occur in the biological systems. Further clinical and experimental studies are required to support the hypothesis of the involvement of boron overexposure in goiter formation. If such association will be confirmed and the potential mechanisms elucidated, it will help to regulate the incidence of hypothyroidism and goiter in endemic regions with high boron levels in soil and water.

Boron workers in China: exploring work and lifestyle factors related to boron exposure.

This article describes the lifestyle patterns of boron mining and processing workers (N=936) and a comparison group (N=251) in northeast China, and explores relationships between boron exposure and reproductive health. An English version of an interview guide addressing areas of work and lifestyle relevant to boron exposure and metabolism was developed by an occupational health research team, translated to Chinese, and translated back, for clarity. Modifications incorporated suggestions from a local community advisory board and boron industry workers; the translation-back translation process was reapplied, and cultural and semantic equivalence was attained. Results from the interviews showed more than 64% of workers and comparison group participants smoked tobacco and more than 92% reported exposure to environmental tobacco smoke. Boron workers and the comparison group varied in their food intake and alcohol consumption, but not in their smoking habits. Thirty-four percent of boron workers reported eating in the contaminated work area. Nearly all boron workers (99%) showered or bathed after work, although approximately 10% redressed in their contaminated clothes. Reproductive health outcomes were explored, including delayed pregnancy, multiple births, spontaneous miscarriages, induced abortions, stillbirths, and an unusual ratio of male to female offspring. Implications for occupational health nurses and recommendations for future research are provided.

Use of boron cluster-containing redox nanoparticles with ROS scavenging ability in boron neutron capture therapy to achieve high therapeutic efficiency and low adverse effects.

A boron delivery system with high therapeutic efficiency and low adverse effects is crucial for a successful boron neutron capture therapy (BNCT). In this study, we developed boron cluster-containing redox nanoparticles (BNPs) via polyion complex (PIC) formation, using a newly synthesized poly(ethylene glycol)-polyanion (PEG-polyanion, possessing a (10)B-enriched boron cluster as a side chain of one of its segments) and PEG-polycation (possessing a reactive oxygen species (ROS) scavenger as a side chain of one of its segments). The BNPs exhibited high colloidal stability, selective uptake in tumor cells, specific accumulation, and long retention in tumor tissue and ROS scavenging ability. After thermal neutron irradiation, significant suppression of tumor growth was observed in the BNP-treated group, with only 5-ppm (10)B in tumor tissues, whereas at least 20-ppm (10)B is generally required for low molecular weight (LMW) (10)B agents. In addition, increased leukocyte levels were observed in the LMW (10)B agent-treated group after thermal neutron irradiation, and not in BNP-treated group, which might be attributed to its ROS scavenging ability. No visual metastasis of tumor cells to other organs was observed 1 month after irradiation in the BNP-treated group. These results suggest that BNPs are promising for enhancing the BNCT performance.

Boron and Coumaphos Residues in Hive Materials Following Treatments for the Control of Aethina tumida Murray.

In the search of alternatives for controlling Aethina tumida Murray, we recently proposed the BAA trap which uses boric acid and an attractant which mimics the process of fermentation caused by Kodamaea ohmeri in the hive. This yeast is excreted in the feces of A. tumida causing the fermentation of pollen and honey of infested hives and releasing compounds that function as aggregation pheromones to A. tumida. Since the boron is the toxic element in boric acid, the aim of this article is to assess the amount of boron residues in honey and beeswax from hives treated with the BAA trap. For this aim, the amount of bioaccumulated boron in products of untreated hives was first determined and then compared with the amount of boron of products from hives treated with the BAA trap in two distinct climatic and soil conditions. The study was conducted in the cities of Padilla, Tamaulipas, and Valladolid, Yucatan (Mexico) from August 2014 to March 2015. The quantity of boron in honey was significantly less in Yucatan than in Tamaulipas; this agrees with the boron deficiency among Luvisol and Leptosol soils found in Yucatan compared to the Vertisol soil found in Tamaulipas. In fact, the honey from Yucatan has lower boron levels than those reported in the literature. The BAA treatment was applied for four months, results show that the BAA trap does not have any residual effect in either honey or wax; i.e., there is no significant difference in boron content before and after treatment. On the other hand, the organophosphate pesticide coumaphos was found in 100% of wax samples and in 64% of honey samples collected from Yucatan. The concentration of coumaphos in honey ranges from 0.005 to 0.040 mg/kg, which are below Maximum Residue Limit (MRL) allowed in the European Union (0.1 mg/kg) but 7.14% of samples exceeded the MRL allowed in Canada (0.02 mg/kg).

Effects of boron supplementation on the severity and duration of pain in primary dysmenorrhea.

BACKGROUND: Primary dysmenorrhea refers to painful menstrual cramps without pelvic pathology. The condition is highly prevalent among women and exerts negative effects on their quality of life. Considering the evidence for anti-inflammatory properties of Boron, the present study aimed to determine the effects of Boron supplementation on the severity and duration of menstrual pain in female university students. METHODS: This triple-blind randomized clinical trial study recruited 113 university students. The participants were matched for the severity and duration of dysmenorrhea and randomly allocated into the case and control groups (n = 58 and 55, respectively). The case group consumed 10 mg/day Boron from two days before the menstrual flow until its third day. The control group received placebo capsules (similar to those distributed among the cases). All subjects were asked to take the capsules for two consecutive menstrual cycles. Pain severity (measured on a visual analog scale) and duration (in hours) were measured at baseline and during the two cycles. RESULTS: The two groups had no significant differences in the severity and duration of pain at baseline. After the intervention, however, the severity and duration of pain were significantly lower in the case group than in the control group (P < 0.05). CONCLUSION: Based on our findings, Boron supplementation can reduce the severity and duration of menstrual pain through exerting anti-inflammatory effects. In order to clarify the effects of Boron on dysmenorrhea, future studies are required to measure the levels of hormones and inflammatory biomarkers.

An assessment of fertility in boron-exposed Turkish subpopulations.

Relationships between elevated boron intake and fertility were sought by comparing reproduction in the residents of two Turkish villages with high levels of boron in their drinking water (one with 8.5 to 29 mg B/L and the other with 2.05 to 2.5 mg B/L), with three nearby villages with more typical low boron levels (0.03 to 0.40 mg B/L). The two high boron villages were designated as Region I, and the three villages with low boron in the drinking water were designated Region II. In addition to exposure to elevated boron in drinking water, 28.3% of the probands in Region I were employed in borate mining or processing, whereas in Region II, 11.7% were so employed. An observational study was carried out in which the authors compared the reproductive history of families living in Region I with families living in Region II by identifying married adults (referred to as probands) who were able to provide information about their and their spouses' family pedigrees covering three generations. Probands were identified by home visits and, if ever married, accepted for ascertainment. Evidence of fertility was birth of a living child, and data were obtained about the fertility of the proband generation, their parents' and also their childrens' generations. In high-boron villages (Region I), 159 three-generation kindreds containing 1068 families were ascertained and, in low-boron villages (Region II), 154 three-generation kindreds containing 610 families were ascertained. In Region 1, 96% of marriages produced at least one child, with primary infertility estimated at 2.34% compared with 96% and 2.62%, respectively, for Region II. There was no significant difference in fertility either between Region I and Region II or between the villages within the Regions. The fertility figures are not different from similar measures of fertility in other parts of Turkey. In Region I, the gender ratio (M:F) of offspring was 0.89, whereas in the Region II villages the gender ratio was 1.04 (NS, chi2 = 1.335, P > 0.05). It is concluded that at the elevated boron drinking water levels studied, a boron-related effect on reproduction was not found.

High concentrations of fluoride and boron in drinking water wells in the Muenster region--results of a preliminary investigation.

In 1998, two cases of severe dental fluorosis in schoolchildren occurred in the Muenster region. These cases took place in one household, where fluoridated toothpaste, fluoridated salt, and fluoride tablets were consumed. Furthermore, the family used drinking water from its private well only. Analyses of the well water ordered by local health officials revealed very high amounts of fluoride, boron, and other electrolytes. This unusual combination of high amounts of fluoride and boron could also be found in the water of a great number of other private wells that are the only source for drinking water in this rural region of the Muensterland. Anthropogenic sources could be excluded. Because of this, the results of the water samples were collated to the specific geological situation in this area. In the Muenster region there are marl layers of the chalk era covered with quarternary sediments. The quarternary sediments are up to 10 to 20 metres thick and they usually conduct the groundwater. The marl contains high concentrations of fluoride and boron. In some places the groundwater has contact with these layers. To check the amount of fluoride and boron in the groundwater, indicator values were sought, which can give a hint of high contents of these trace elements. In this study the conductivity and acidity were identified as possible indicators of a high amount of fluoride and boron in the drinking water in this specific region. To work economically and efficiently, the drinking water should be checked for fluoride and boron on a regular basis only when these values are extraordinarily high. In the case of high concentrations, especially of fluoride, in the drinking water the persons concerned should be informed about their potential health risk, giving them the opportunity to optimise the total daily intake of fluoride.

The isotopic composition of anthropogenic boron and its potential impact on the environment.

The present study investigates the isotopic composition of anthropogenic boron (B) and its potential affects on the environment. The isotopic ratios of B in synthetic products from the main ores in the world have been measured by negative thermal ionization mass spectrometry. The data show that the isotopic compositions of Na-borate products and washing powders overlap with those of natural Na-borate minerals. In contrast, the 11B/10B ratios of synthetic Ca-borate and Na/Ca borate products are significantly lower (by 15 permil) and overlap with those of the natural Ca-borate minerals. Consequently, the original isotopic signature of natural borate minerals is not modified during the manufacturing process of synthetic products. The B isotopic composition of domestic wastewater from Israel and Riverside, California suggests that B in sewage is derived from Na-borate components used in detergents. Since B, like other inorganic ions, is not removed during conventional sewage treatment, it accumulates in domestic wastewater. Although the B concentration in pristine groundwaters is generally low (<0.05 mg/L), contaminant sources (e.g., wastewater) are relatively enriched in B (0.5-1 mg/L). The isotopically distinguished signature of borate compounds is used to trace groundwater contamination.

International Programme on Chemical Safety (IPCS) environmental health criteria on boron human health risk assessment.

The International Program on Chemical Safety (IPCS), a collaborative program of the United Nations Environment Program, the International Labour Organization (ILO), and the World Health Organization (WHO), includes the Environmental Health Criteria (EHC) Program inaugurated in 1973 by WHO. These EHC are integrated evaluations of the human health and environmental risks from exposure to specific chemicals carried out by a group of international scientists. Boron (B) was evaluated at an IPCS Task Group (TG) convened in November 1996. All TGs are convened under WHO rules and procedures. These procedures relate the overall process used to prepare an EHC including transparency of the process, conflict of interest, the roles of Members and Observers, and the conduct of the TG. The scope and purpose of an EHC, for an element such as B, and its possible role in national and international chemical safety programs will be discussed. In the early 1990s, countries asked that IPCS request TGs to prepare, where data permit, health-based guidance values (GVs) (both total daily intake and to recommend health-based guidelines for various environmental media). This final evaluation in an EHC reflects the collective consensus view of the TG Members. To foster the use of consistent methodology by TGs, IPCS prepared in 1994 an EHC on the methodology for the preparation of GVs for human exposure limits (EHC 170). In developing their final evaluation, TGs have been asked to consider using this methodology. This was done by the TG on B, and a total daily intake for humans of 0.4 mg/kg body wt was derived from animal studies of reproductive and developmental effects in rodents and pharmacokinetic data from both animals and humans. The application of the methodology described in EHC 170 regarding choice of critical effect and uncertainty factors will be discussed.

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.

The nutritional and metabolic effects of boron in humans and animals.

We have undertaken studies in humans and animals that aimed to obtain further information about the intake and excretion of boron (B) as well as its effects on markers of coronary heart disease. In humans, we have shown that the intake of B is 2.2 mg/d; its urinary excretion is 1.9 mg/d, and there appears to be little intraindividual variation. Supplementation with 10 mg of B/d resulted in the recovery of 84% of the dose in the urine and a significant increase in plasma estradiol concentration, but no effect on plasma lipoproteins. In rats, increasing the intake of B through the drinking water is reflected in the tissue concentrations, results in an increase in plasma testosterone and vitamin D, and results in a decrease in HDL cholesterol. It is clear that B has the potential to impact significantly on a number of metabolic processes.