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.

Evaluation of FSH, LH, testosterone levels and semen parameters in male boron workers under extreme exposure conditions.

Boric acid and sodium borates are currently classified in the EU-CLP regulation as "toxic to reproduction" under "Category 1B", with hazard statement of H360FD. However, so far field studies on male reproduction in China and in Turkey could not confirm such boron-associated toxic effects. As validation by another independent study is still required, the present study has investigated possible boron-associated effects on male reproduction in workers (n = 212) under different boron exposure conditions. The mean daily boron exposure (DBE) and blood boron concentration of workers in the extreme exposure group (n = 98) were 47.17 ± 17.47 (7.95-106.8) mg B/day and 570.6 ± 160.1 (402.6-1100) ng B/g blood, respectively. Nevertheless, boron-associated adverse effects on semen parameters, as well as on FSH, LH and total testosterone levels were not seen, even within the extreme exposure group. With this study, a total body of evidence has accumulated that allows to conclude that male reproductive effects are not relevant to humans, under any feasible and realistic conditions of exposure to inorganic boron compounds.

Genotoxicity in humans exposed to arsenic, lithium, and boron in drinking water in the Bolivian Andes-A cross sectional study.

Elevated concentrations of arsenic, lithium and boron in drinking water have already been reported in Bolivia. Arsenic is known to cause genotoxicity but that caused by lithium and boron is less well known. The aim of the present cross-sectional study was to evaluate potential genotoxic effects of exposure to arsenic, while considering exposure to lithium and boron and genetic susceptibility. Women (n = 230) were recruited in villages located around Lake Poopó. Exposure to arsenic was determined as the sum of concentrations of arsenic metabolites inorganic arsenic, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) in urine. Exposure to lithium and boron was determined based on their concentrations in urine. Genetic susceptibility was determined by GSTM1 (glutathione S-transferase-mu-1) and GSTT1 (glutathione S-transferase-theta-1) null genotypes and AS3MT (Arsenite Methyltransferase) rs3740393. Genotoxicity was measured in peripheral blood leukocytes using the comet assay. The geometric means of arsenic, lithium, and boron concentrations were 68, 897, and 3972 µg/L, respectively. GSTM1 and GSTT1 null carriers had more DNA strand breaks than gene carriers (p = .008, p = .005). We found no correlation between urinary arsenic and DNA strand breaks (rS = .03, p = .64), and only a weak non-significant positive association in the adjusted multivariate analysis (ß = .09 [-.03; .22], p = .14). Surprisingly, increasing concentrations of lithium in urine were negatively correlated with DNA strand breaks (rS = -.24, p = .0006), and the association persisted in multivariate analysis after adjusting for arsenic (ß = -.22 [-.36; -.08], p = .003). We found no association between boron and DNA strand breaks. The apparent protective effect of lithium merits further investigation.

[Comparative study of the urinary excretion of boron, calcium, magnesium and phosphorus in postmenopausal women with and without osteoporosis]. / Estudio comparativo de la excreción urinaria de boro, calcio, magnesio y fósforo en mujeres posmenopáusicas con y sin osteoporosis.

In order to compare the possible relationship between urinary concentrations of boron, calcium, magnesium and phosphorus in serum and urine of postmenopausal women with and without osteoporosis, we selected 45 postmenopausal women over 47 years of age, divided into two groups: group I clinically healthy postmenopausal women and group II postmenopausal women with osteoporosis, without chronic kidney and hepatic diseases or diabetes mellitus. We determined the boron (B), phosphorus (P), total calcium (Ca) and total magnesium (Mg) in the urine of two hours, by atomic emission spectroscopy with induction-coupled plasma (ICPA-ES). Total calcium and total magnesium in serum were determined by atomic flame absorption spectroscopy (FAAS) and inorganic phosphorus in serum, and creatinine in serum and urine, by molecular absorption spectrometry. The preliminary results suggest the existence of a significant difference (p < 0.05) in boron and phosphorus concentrations in the urine of two hours between the groups. The model of linear regression analysis used showed a relationship between urinary concentrations of boron/creatinine index and calcium/ creatinine, magnesium/creatinine and phosphorus/creatinine indexes in the urine of postmenopausal women with osteoporosis.

Reproductive toxicity parameters and biological monitoring in occupationally and environmentally boron-exposed persons in Bandirma, Turkey.

Boric acid and sodium borates have been considered as being "toxic to reproduction and development", following results of animal studies with high doses. Experimentally, a NOAEL (no observed adverse effect level) of 17.5 mg B/kg-bw/day has been identified for the (male) reproductive effects of boron in a multigeneration study of rats, and a NOAEL for the developmental effects in rats was identified at 9.6 mg B/kg-bw/day. These values are being taken as the basis of current EU safety assessments. The present study was conducted to investigate the reproductive effects of boron exposure in workers employed in boric acid production plant in Bandirma, Turkey. In order to characterize the external and internal boron exposures, boron was determined in biological samples (blood, urine, semen), in workplace air, in food, and in water sources. Unfavorable effects of boron exposure on the reproductive toxicity indicators (concentration, motility, morphology of the sperm cells and blood levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone) were not observed. The mean calculated daily boron exposure (DBE) of the highly exposed group was 14.45 ± 6.57 (3.32-35.62) mg/day. These human exposures represent worst-case exposure conditions to boric acid/borates in Turkey. These exposure levels are considerably lower than exposures, which have previously led to reproductive effects in experimental animals. In conclusion, this means that dose levels of boron associated with developmental and reproductive toxic effects in animals are by far not reachable for humans under conditions of normal handling and use.

Boron Contents of German Mineral and Medicinal Waters and Their Bioavailability in Drosophila melanogaster and Humans.

SCOPE: Boron is a trace element that naturally occurs in soil, making mineral and medicinal water important contributors to overall intake. Thus, in a systematic screening, the mean boron concentrations of 381 German mineral and medicinal waters are determined. METHODS AND RESULTS: Boron concentrations in mineral and medicinal waters are analyzed by inductively coupled mass spectrometry (ICP-MS). Highest boron values find in waters from the southwest of Germany. The boron content of the waters is positively correlated with the concentration of most other analyzed bulk elements, including calcium, potassium, magnesium, and sodium. Mineral waters with either low (7.9 µg L-1 ), medium (113.9 µg L-1 ), or high (2193.3 µg L-1 ) boron content are chosen for boron exposure experiments in fruit flies (Drosophila melanogaster) and humans. In flies, boron-rich mineral water significantly increases boron accumulation, with the accumulation predominantly occurring in the exoskeleton. In humans, serum boron and 24-h urinary boron excretion significantly increase only in response to the intake of boron-rich mineral water. CONCLUSION: Overall, the current data demonstrate that mineral and medicinal waters vary substantially in the content of boron and that boron-rich mineral water can be used to elevate the boron status, both in flies and humans.

High-level exposure to lithium, boron, cesium, and arsenic via drinking water in the Andes of northern Argentina.

Elevated concentrations of arsenic in drinking water are common worldwide, however, little is known about the presence of other potentially toxic elements. We analyzed 31 different elements in drinking water collected in San Antonio de los Cobres and five surrounding Andean villages in Argentina, and in urine of the inhabitants, using ICP-MS. Besides confirmation of elevated arsenic concentrations in the drinking water (up to 210 microg/L), we found remarkably high concentrations of lithium (highest 1000 microg/L), cesium (320 microg/L), rubidium (47 microg/L), and boron (5950 microg/L). Similarly elevated concentrations of arsenic, lithium, cesium, and boron were found in urine of the studied women (N=198): village median values ranged from 26 to 266 microg/L of arsenic, 340 to 4550 microg/L of lithium, 34 to 531 microg/L of cesium, and 2980 to 16,560 microg/L of boron. There is an apparent risk of toxic effects of long-term exposure to several of the elements, and studies on associations with adverse human health effects are warranted, particularly considering the combined, life-long exposure. Because of the observed wide range of concentrations, all water sources used for drinking water should be screened for a large number of elements; obviously, this applies to all drinking water sources globally.

Boron-rich diet may regulate blood lipid profile and prevent obesity: A non-drug and self-controlled clinical trial.

BACKGROUND: Boron is an element commonly found in nature. The main boron source for organisms is through food and drinking water. In recent years, it is suggested that the "boron-rich diet" can affect human health positively. However, more detailed studies are needed. OBJECTIVE: The aim of this study was to examine the effect of increased dietary boron intake on some biochemical parameters in humans. MATERIAL AND METHODS: Thirteen healthy women consumed diets containing 10 mg more boron than their routine diet for one month. This boron intake was provided with the increase of boron-rich foods such as dried fruits, avocado, and nuts in the diet. Some biochemical and hematologic parameters were determined in blood, urine and saliva samples taken before and after a boron-rich diet. RESULTS: Serum, salivary, and urine boron concentrations increased 1.3, 1.7, 6.0 fold, respectively. The most significant clinically change was found in the lipid profile. Serum total, LDL, VLDL cholesterol, and triglyceride levels decreased significantly. Body weight, body fat weight, and Body Mass Index also decreased. Significant changes in serum TSH and salivary buffering capacity were also found. CONCLUSION: Increasing the intake of boron through dietary means might contribute to beneficial effects on lipid metabolism, obesity, and thyroid metabolism; salivary boron may reflect serum boron; and boron may be used as a cariostatic agent in dentistry. An increased intake of other dietary factors such as fiber, potassium, iron, vitamin A, and vitamin E in the boron-rich foods might have been responsible of the effects described. To our knowledge, this study is the first clinical study in which dietary boron intake is increased via foods.

Trace element loss in urine and effluent following traumatic injury.

BACKGROUND: Few data are available to establish recommendations for trace element supplementation during critical illness. This study quantified the loss of several elements and assessed the adequacy of manganese and selenium in parenteral nutrition (PN). METHODS: Men with traumatic injuries were grouped by renal status: adequate (POLY; n = 6), acute failure with continuous venovenous hemofiltration (CVVH; n = 2), or continuous venovenous hemodiafiltration (CVVHD; n = 4). PN supplied 300 microg/d manganese and 60 microg/d selenium. Urine and effluent (from artificial kidneys) were collected for 3 days and analyzed for boron, manganese, nickel, and silicon using inductively coupled plasma atomic emission spectrometry, and for selenium using atomic absorption spectrometry. RESULTS: POLY manganese and selenium excretion averaged (standard deviation [SD]) 7.9 (3.3) microg/d and 103.5 (22.4) microg/d, respectively. All elements except selenium were detected in dialysate (prior to use). CVVHD effluent contained 3.5 and 7.3 times more manganese and nickel than CVVH ultrafiltrate, respectively. Loss of manganese averaged 2.6%, 21%, and 73% of PN amounts for POLY, CVVH, and CVVHD groups, respectively. DISCUSSION: Minimal loss of manganese compared with the amount in PN suggests that excessive amounts are retained. POLY patients excreted more selenium than was in PN, indicating negative balance. POLY losses of boron and silicon were less than that published for healthy adults, reflecting less than typical intake, whereas loss during CVVH was in the normal reference range, possibly because of added intake from boron contamination of replacement fluids. All patients lost more nickel than amounts published for healthy adults. CONCLUSIONS: Current guidelines of 60-100 microg/d of parenteral manganese may be excessive for trauma patients. The uptake of manganese and nickel from contaminants in CVVHD dialysate should be investigated.

Biomarkers of environmental and workplace boron exposure.

The purpose of this work was to identify an accurate, noninvasive biomarker of boron exposure that could be used in worker populations. Occupational exposure to boron is of concern due to high numbers of workers exposed, animal toxicity data suggesting reproductive effects, and lack of human studies. Total daily boron exposure was determined from duplicate samples of 24-hr food and fluid intake, plus workplace personal air monitoring in boron workers and comparison groups in northern China during 2003 and 2004. Boron was also measured in blood, semen, creatinine-corrected postshift urine, and 24-hr urine. Total daily boron exposure (mg/day) averaged 41.2 for men working in the boron industry and 2.3 for the comparison group. Boron concentration in postshift urine was correlated with 24-hr urine boron concentration (Pearson correlation coefficient = 0.85, p < 0.0001). Boron concentration in postshift urine was correlated with total daily boron exposure measured through food, fluid, and personal air monitoring (Pearson correlation coefficient = 0.83, p < 0.0001). Boron concentration in postshift urine was also correlated with internal dose measures of boron in blood and semen (Pearson correlation coefficient = 0.85, 0.80 respectively, p < 0.0001). This work suggests that creatinine-corrected, postshift urine boron concentration can be used as a biomarker of human boron exposure in worker populations.

Biomonitoring of boron: Development and characterization of a simple, reliable and quality controlled biomonitoring method.

Boron exposure is of interest and concern from an occupational point of view. Usual daily boron intake is related to boron blood plasma concentration <1mg/L and to <3mg/L in urine, but after exposure urine concentrations are quickly elevated. Reliable boron biomonitoring, typically in urine, thus is mandatory for occupational health control institutions. This paper reports on the development of a simple, fast and reliable boron determination procedure based on inductively coupled plasma - optical emission spectrometry (ICP-OES). Major aims for this method were simplicity in sample preparation, low risk for artifacts and interferences, high precision and accuracy, possibly low costs, including lower costs for element selective detection, short total analysis time and suitability for occupational health laboratories. Precision data (serial or day-to-day) from urine and doped urine were very good: <1.5 or <2%. Accuracy was calculated from analysis of a certified reference material (ERM-CD 281), as 99% or according to recoveries of doped concentrations ranging from 102 to 109% recovery. For cross-checking ICP-OES determinations, samples were analyzed also by quadrupole ICP-qMS and by sectorfield ICP-sf-MS at low and medium resolution. Both systems confirmed ICP-OES measurements when using 11B for quantification. Determinations based on 10B however showed some bias, except with ICP-sf-MS at medium resolution. The observed elevated signals are discussed with respect to the known Ne++ interference (as an impurity in Ar), which is not separated in low resolving quadrupole ICP-MS systems or ICP-sf-MS at low resolution.

Relationship Not Found Between Blood and Urine Concentrations and Body Mass Index in Humans With Apparently Adequate Boron Status.

The impact of boron on the development of obesity remains controversial in the analysis of experimental and clinical data. The objective of this study was to investigate the relationship between blood and urine boron concentrations and obesity in normal, overweight, obese, and morbidly obese subjects in different age groups. A total of 105 subjects were categorized into 12 groups based on body mass index and three different age levels: as young adult (18 to 34 years old), adult (35 to 54 years old), and older adult (greater than 55 years old). Age, gender, body mass index, and blood and urine boron concentrations were recorded for each subject. There were 50 women and 55 men, with a mean age of 44.63 ± 17.9 years. Blood and urine boron concentrations were similar among the groups (p = 0.510 and p = 0.228, respectively). However, a positive correlation between age and blood boron concentration (p = 0.001) was detected in contrast to the presence of a negative correlation between age and urine boron concentration (p = 0.027). Multiple linear regression analysis showed that there was no significant relationship between gender, age, and quantitative values of body mass index for each subject, and blood and urine boron concentrations. Although the relationship between boron and obesity has not been confirmed, changes of blood and urine boron concentrations with age may have some physiologic sequences to cause obesity.

Is Boric Acid Toxic to Reproduction in Humans? Assessment of the Animal Reproductive Toxicity Data and Epidemiological Study Results.

Boric acid and sodium borates are classified as toxic to reproduction in the CLP Regulation under "Category 1B" with the hazard statement of "H360FD". This classification is based on the reprotoxic effects of boric acid and sodium borates in animal experiments at high doses. However, boron mediated reprotoxic effects have not been proven in epidemiological studies so far. The epidemiological study performed in Bandirma boric acid production plant is the most comprehensive published study in this field with 204 voluntarily participated male workers. Sperm quality parameters (sperm morphology, concentration and motility parameters), FSH, LH and testosterone levels were determined in all participated employees as the reproductive toxicity biomarkers of males. However, boron mediated unfavorable effects on reproduction in male workers have not been determined even in the workers under very high daily boron exposure (0.21 mg B/kg-bw/day) conditions. The NOAEL for rat reproductive toxicity is equivalent to a blood boron level of 2020 ng/g. This level is higher than the mean blood boron concentration (223.89 ± 69.49 ng/g) of the high exposure group workers in Bandirma boric acid production plant (Turkey) by a factor of 9. Accordingly, classifying boric acid and sodium borates under "Category 1B" as "presumed reproductive human toxicant in the CLP regulation seems scientifically not reasonable. The results of the epidemiological studies (including the study performed in China) support for a down-classification of boric acid from the category 1B, H360FD to category 2, H361d, (suspected of damaging the unborn child).

Effect of boron supplementation on blood and urinary calcium, magnesium, and phosphorus, and urinary boron in athletic and sedentary women.

It has been reported that boron may be beneficial for optimal calcium metabolism and, thus, optimal bone metabolism. Therefore, we designed a study to determine the effects of boron supplementation on blood and urinary minerals in athletic subjects and sedentary control subjects consuming self-selected typical Western diets. Serum phosphorus concentrations were lower in boron-supplemented subjects than in placebo-supplemented subjects. Compared with all other subjects, serum magnesium concentrations were greatest in the sedentary control subjects supplemented with boron and increased with time in all subjects. Exercise training diminished changes in serum phosphorus concentrations caused by boron supplementation. Calcium excretion increased over time in all groups combined, and boron excretion increased over time in all boron-supplemented subjects. The findings suggest that boron supplementation modestly affected mineral status, and exercise modified the effects of boron supplementation on serum minerals.

The relationship of blood- and urine-boron to boron exposure in borax-workers and usefulness of urine-boron as an exposure marker.

Daily dietary-boron intake and on-the-job inspired boron were compared with blood- and urine-boron concentrations in workers engaged in packaging and shipping borax. Fourteen workers handling borax at jobs of low, medium, and high dust exposures were sampled throughout full shifts for 5 consecutive days each. Airborne borax concentrations ranged from means of 3.3 mg/m3 to 18 mg/m3, measured gravimetrically. End-of-shift mean blood-boron concentrations ranged from 0.11 to 0.26 microgram/g; end-of-shift mean urine concentrations ranged from 3.16 to 10.72 micrograms/mg creatinine. Creatinine measures were used to adjust for differences in urine-specific gravity such that 1 ml of urine contains approximately 1 mg creatinine. There was no progressive increase in end-of-shift blood- or urine-boron concentrations across the days of the week. Urine testing done at the end of the work shift gave a somewhat better estimate of borate exposure than did blood testing, was sampled more easily, and was analytically less difficult to perform. Personal air samplers of two types were used: one, the 37-mm closed-face, two-piece cassette to estimate total dust and the other, the Institute of Occupational Medicine (IOM) sampler to estimate inspirable particulate mass. Under the conditions of this study, the IOM air sampler more nearly estimated human exposure as measured by blood- and urine-boron levels than did the sampler that measured total dust.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of pregnancy on renal clearance of boron in humans: a study based on normal dietary intake of boron.

Boron occurs most frequently in nature as borates and boric acid, never as the free element. Its largest uses are in glass, detergents, and agriculture. Essential for higher plants, there is growing evidence for essentiality in vertebrates. Humans consume daily about a milligram of boron, mostly from fruit and vegetables. At high doses, boron is a developmental and reproductive toxin in animals. Pregnant rats were the most sensitive. An oral NOAEL of 9.6 mg B/kg/day was established for developmental toxicity in Sprague-Dawley rats fed boric acid. To extrapolate from the large, animal boron toxicity database to humans, especially to pregnant women, information on renal clearance of boron was needed. This study's purpose was to measure renal clearance of boron in pregnant and nonpregnant woman. In 16 second trimester women and 15 nonpregnant age-matched referents, dietary boron provided the blood and urine boron concentrations used for calculating boron clearance. The pregnant and nonpregnant boron intake was 1.35 and 1.31 mg boron/24 h, respectively. Blood for boron, creatinine, and urea was collected at the start, at 2 h, and at 24 h. Urine was collected during the first 2 h in the Clinical Research Center and during a 22-h period outside the center for measurement of volume, boron, and creatinine. Renal boron clearance measured over the initial 2 h, the most complete urine collection period, was 68.30ml/min/1.73 m(2) for pregnant subjects and 54.31ml/min/1.73 m(2) for nonpregnant subjects. Comparison of renal boron clearance with creatinine clearance indicated that tubular reabsorption of boron occurred in both pregnant and nonpregnant women.

The effect of pregnancy on renal clearance of boron in rats given boric acid orally.

Boric acid (H(3)BO(3)) has been shown to cause developmental abnormalities in the offspring of pregnant rats. Comparative data on the renal clearance of boron (B) in rats and humans, both pregnant and nonpregnant, exposed to boric acid (BA) would reduce uncertainty in interspecies extrapolation from rats to humans. The purpose of this study was to evaluate the effect of pregnancy on the plasma half-life and renal clearance of boron in Sprague-Dawley rats given a single oral dose of boric acid. For the half-life study, nonpregnant and pregnant (gestation day 16) rats were given a single dose of 30 mg/kg of boric acid by gavage, and plasma samples were collected at 2-3 h intervals. The plasma half-life of boron was determined to be 2.9 +/- 0.2 and 3.2 +/- 0.3 h in nonpregnant and pregnant rats, respectively. In the clearance study, nonpregnant and pregnant (GD 16) rats were given a single gavage dose of 0.3, 3, or 30 mg/kg of boric acid. Boron clearance was slightly higher in pregnant rats (3.3 +/- 0.6, 3.2 +/- 0.5, and 3.4 +/- 0.5 ml/min/kg, respectively) compared to nonpregnant rats (3.1 +/- 0.8, 3.0 +/- 0.6, and 3.2 +/- 0.5 ml/min/kg, respectively), but the difference was not statistically significant and not dose-related. Boron clearance was less than creatinine clearance, suggesting tubular reabsorption in both groups. In conclusion, pregnancy did not appear to significantly alter the renal clearance or the plasma half-life of boron in Sprague-Dawley rats under the conditions of this study.

Human disodium octaborate tetrahydrate exposure following carpet flea treatment is not associated with significant dermal absorption.

Disodium octaborate tetrahydrate is used for indoor flea control on carpets and furniture. Disodium octaborate tetrahydrate was applied to a 100% nylon carpet as a solution using a powered rug brush at a rate of approximately 200 micrograms/cm2 carpet. Two randomly chosen groups of volunteers (18 females, 4 males) wore either bathing suits which provided 75% or more skin exposure or whole-body, cotton dosimeters consisting of socks, union suits, and gloves. The volunteers performed a 20-minute set of Jazzercise routines. The availability of boron was demonstrated by covering portions of the carpet with a cotton dosimeter and rolling it with a weighted roller. Additionally, disodium octaborate tetrahydrate was transferred to the whole-body dosimeter. Volunteers also collected 24-hour urine specimens prior to and following the exercise period. The specimens were analyzed for total boron by inductively coupled plasma emission spectroscopy. No evidence of contact transfer and dermal absorption was obtained. The mean daily boron levels (mg/g creatinine) were 1.17, 1.33, and 1.31 for the group with exposed skin and 1.26, 1.12, and 1.26 for those who wore dosimeters which prevented contact. Daily urine boron levels were not significantly different when compared using a two sample t-test assuming equal variances (P > 0.05). Direct dermal contact with disodium octaborate tetrahydrate-treated carpet at a nominal rate of 200 micrograms/cm2 did not produce any adverse effects or change urinary boron clearance.

Study on urine boron reference values of Japanese men: use of confidence intervals as an indicator of exposure to boron compounds.

A simple and rapid method for the determination of urine boron by inductively-coupled plasma argon emission spectrometry (ICPAES) has been developed to establish boron exposure guidelines. After 11-fold dilution in 18.25 M omega cm ultra-pure water and vigorous shaking, urine may be directly injected into the spectrometer, providing accurate and reproducible results. We report the results obtained with urine samples obtained from a group of male Japanese electronic workers (n = 102) who had not been exposed to boron; boron concentrations were corrected with use of a specific gravity of 1.024 g/ml. The frequency distribution resulted in a log-normal distribution diagram for anatomical spread. The geometric mean values for urine boron in the non-exposed workers was 798.0 micrograms/l, while the confidence interval (C.I.) was between 398.1 and 1599.6 micrograms/l. Taking into consideration the short biological half-life of boron and its major excretion route via urine, urine was considered to be a suitable means for monitoring of exposure to this element. We conclude that the guidelines established by determining boron reference values are useful for the protection of individuals exposed to boron in their working environments.

Distribution and excretion of boron after intravenous administration of disodium mercaptoundecahydro-closo-dodecaborate to rats.

Disodium mercaptoundecahydro-closo-dodecaborate (BSH) is an important compound for boron neutron capture therapy. The pharmacokinetics of boron by BSH were studied in normal rats after rapid intravenous injection at three doses (30, 100, 300 mg/kg) or continuous infusion (100 mg/kg/30 min). The boron concentration in biological samples was measured by inductively coupled plasma atomic emission spectroscopy. The blood half-lives of boron in the elimination phase (t1/2 beta) after rapid injection of BSH at doses of 30, 100 and 300 mg/kg were 1.7, 17 and 19 hr, respectively. AUC (32, 219 and 4030 micrograms.hr/ml) increased with the dose, but there was no proportionality among the values. Total clearance decreased drastically from 233 ml/hr/kg (100 mg/kg) to 38 ml/hr/kg (300 mg/kg). As boron was excreted mainly into urine, these results suggest that renal function failure might occur with dosing of 300 mg/kg. In the case of continuous infusion of 100 mg/kg of BSH for 30 min, the pharmacokinetic parameters were similar to those of rapid injection of 100 mg/kg. The highest boron concentration was observed in the kidney and the lowest in the brain. After multiple dosing of BSH at 100 mg/kg/day x 14 days, the boron concentrations in blood, liver, lung and kidney at 24 hr after the last dosing were higher than those after single dosing and were similar to those of simulated values calculated from the single dosing parameters. These results clearly indicated that boron does not accumulate unexpectedly in any tissue with multiple dosing of 100 mg/kg of BSH for two weeks.