Pharmacokinetics of bisphenol A in humans following a single oral administration

BackgroundHuman exposures to bisphenol A (BPA) are widespread. The current study addresses uncertainties regarding human pharmacokinetics of BPA.ObjectiveTo reduce uncertainties about the metabolism and excretion of BPA in humans following oral administration.MethodsWe exposed six men and eight women to 100 μg/kg bw of deuterated BPA (d6-BPA) by oral administration and conducted blood and urine analysis over a three day period. The use of d6-BPA allowed administered d6-BPA to be distinguished from background native (unlabeled) BPA. We calculated the rate of oral absorption, serum elimination, half-life, area under the curve (AUC), urinary excretion, and metabolism to glucuronide and sulfate conjugates.ResultsMean serum total (unconjugated and conjugated) d6-BPA C_max of 1711 nM (390 ng/ml) was observed at T_max of 1.1 ± 0.50 h. Unconjugated d6-BPA appeared in serum within 5–20 min of dosing with a mean C_max of 6.5 nM (1.5 ng/ml) observed at T_max of 1.3 ± 0.52 h. Detectable blood levels of unconjugated or total d6-BPA were observed at 48 h in some subjects at concentrations near the LOD (0.001–0.002 ng/ml). The half-times for terminal elimination of total d6-BPA and unconjugated d6-BPA were 6.4 ± 2.0 h and 6.2 ± 2.6 h, respectively. Recovery of total administered d6-BPA in urine was 84–109%. Most subjects (10 of 14) excreted > 90% as metabolites within 24 h.ConclusionsUsing more sensitive methods, our study expands the findings of other human oral pharmacokinetic studies. Conjugation reactions are rapid and nearly complete with unconjugated BPA comprising less than 1% of the total d6-BPA in blood at all times. Elimination of conjugates into urine largely occurs within 24 h.     

Critical compilation and review of plant/soil concentration ratios for uranium,thorium and lead

The transfer of natural radionuclides of the U decay series through the biosphere is important, especially for assessment of the impacts of mining and milling of U ores. The pathway from soil through plants to humans can contribute significantly to the overall dose received from these radionuclides. Element-specific concentration ratios (CRs) used to model the impact of radionuclides have been reported for U, Th and Pb but have not received the research or critical review accorded other radionuclides associated with the nuclear industry. This paper compiles and analyses many of the available data on CRs for U, Th and Pb and recommends values appropriate for environmental assessments. A brief overview of the statistical properties of CR values and the complex soil/plant processes encompassed by this ratio is also given, as well as an overview of some of the physical, chemical and biological factors likely to influence CR values.Our analysis showed that CR values decreased significantly as the corresponding soil concentrations increased. Although the variability was substantial, with ranges of 1000- to 30 000-fold, CR values did differ significantly among some soil and plant types. The overall geometric means were 0·0045, 0·0036 and 0·052 for U, Th and Pb, respectively.     

Preliminary evaluation of PAH sorptive changes in soil by Soxhlet extraction

This study was conducted to evaluate the influence of sorbent modification by synthetic, chemical/thermal weathering on the sorptive behavior of polycyclic aromatic hydrocarbons (PAHs). A clean sandy-clay-loam soil was subjected to Soxhlet extraction and PAH sorptive phenomena were evaluated based on quantity and quality changes in soil organic matter (SOM) and clay minerals. Critical changes in sorption capacity were found to depend on the initial PAH concentrations. Above 7 mg/l, weathering increased the PAH in comparison to that of unmodified soil, whereas it decreased when applied below this concentration. Similarly, less PAH was desorbed from the altered soil when PAH was applied above 7 mg/l. Therefore, when PAH was applied below 7 mg/l, quantitative reduction of sorbent amount (i.e., SOM and clay minerals) by soil weathering governed PAH sorptive behavior. However, when the PAH was applied above the critical limit, qualitative modifications in the sorbents facilitated an opposite trend. Sorbent swelling, removal of competing compounds, and possible changes in surface characteristics by Soxhlet extraction, together with increased concentration gradient effects were factors that resulted in dissimilar PAH sorptive phenomena, pivoting at the critical concentration.     

French children's exposure to metals via ingestion of indoor dust,outdoor playground dust and soil: Contamination data

In addition to dietary exposure, children are exposed to metals via ingestion of soils and indoor dust, contaminated by natural or anthropogenic outdoor and indoor sources. The objective of this nationwide study was to assess metal contamination of soils and dust which young French children are exposed to. A sample of 484 children (6 months to 6 years) was constituted in order to obtain representative results for young French children. In each home indoor settled dust was sampled by a wipe in up to five rooms. Outdoor playgrounds were sampled with a soil sample ring (n = 315) or with a wipe in case of hard surfaces (n = 53). As, Cd, Cr, Cu, Mn, Pb, Sb, Sr, and V were measured because of their potential health concern due to soil and dust ingestion. The samples were digested with hydrochloric acid, and afterwards aqua regia in order to determine both leachable and total metal concentrations and loadings by mass spectrometry with a quadrupole ICP-MS. In indoor settled dust most (total) loadings were below the Limit of Quantification (LOQ), except for Pb and Sr, whose median loadings were respectively 9 and 10 μg/m². The 95th percentile of loadings were 2 μg/m² for As, < 0.8 for Cd, 18 for Cr, 49 for Cu, < 64 for Mn, 63 for Pb, 2 for Sb, 56 for Sr, and < 8 for V. Median/95th percentile of loadings in settled dust on outdoor playgrounds were 2/16, < 0.8/1.3, 17/53, 49/330, 99/424, 32/393, 2/13, 86/661 and 10/37 μg/m² for As, Cd, Cr, Cu, Mn, Pb, Sb, Sr, and V respectively. In outdoor playground soil median/95th percentile of concentrations (μg/g) were 8/26, < 0.65/1, 25/52, < 26/53,391/956, 27/254, 0.7/4, 54/295, 23/57 for As, Cd, Cr, Cu, Mn, Pb, Sb, Sr, and V respectively. These results are comparable with those observed in other countries. Because of their representative nature, we can assess children's exposures to these metals via soil and dust and the associated risks in urban and rural environments. Ratios of leachable/total concentrations and loadings, calculated on > LOQ measurements, differed among metals. To a lesser extent, they were also affected by type of matrix, with (except for Cd) a greater leachability of dust (especially indoor) compared to soils.     

Spatial distribution of uranium and thorium in the surface soil around proposed uranium mining site at Lambapur and its vertical profile in the Nagarjuna Sagar Dam

The understanding and evaluation of the possible interactions of various naturally occurring radionuclides in the world's third largest man-made dam, Nagarjuna Sagar located in Andhra Pradesh, India and built on river Krishna assumed significance with the finding of uranium deposits in locations near the dam. For the present work, surface soil samples from the mineralized area of Lambapur, Mallapuram, Peddagattu and sediment core samples from the Nagarjuna Sagar dam were analyzed for naturally occurring radionuclides namely uranium and thorium using gamma spectrometric technique. Also toxic elements lead and chromium were analysed by the Energy Dispersive X-ray Fluorescence Spectrometer (EDXRF) technique. Surface soil samples show a variation from 25 to 291 Bq/kg (2.02–23.5 mg/kg) for ²³⁸U and 32–311 Bq/kg (7.9–76.9 mg/kg) for ²³²Th. U/Th concentration ratio in surface soil samples ranged from 0.19 to 0.31 and was found comparable with the nation wise average of 0.26. The study of sediment core samples reflected higher U/Th concentration ratio of 0.30–0.33 in the bottom section of the core as compared to 0.22–0.25 in the upper section. The concentration ratio in the upper section of the core was similar to the ratio 0.23 found in the western Deccan Basalt region through which the river originates. A higher concentration of lead and chromium was observed in the upper section of the core compared to bottom section indicating the impact of river input on the geochemical character of dam sediment.     

Intercomparison of model predictions of tritium concentrations in soil and foods following acute airborne HTO exposure

This paper describes the results of a model intercomparision exercise for predicting tritium transport through foodchains. Modellers were asked to assume that farmland was exposed for one hour to an average concentration in air of 10⁴ MBq tritium m^-3. They were given the initial soil moisture content and 30 days of hourly averaged historical weather and asked to predict HTO and OBT concentrations in foods at selected times up to 30 days later when crops were assumed to be harvested. Two fumigations were postulated, one at 10.00 h (i.e., in day-light), and the other at 24.00 h (i.e., in darkness).Predicted environmental media concentrations after the daytime exposure agreed within an order of magnitude in most cases. Important sources of differences were variations in choices of numerical values for transport parameters. The different depths of soil layers used in the models appeared to make important contributions to differences in predictions for the given scenario. Following the night-time exposure, however, greater differences in predicted concentrations appeared. These arose largely because of different ways key processes were assumed to be affected by darkness. Uptake of HTO by vegetation and the rate it is converted to OBT were prominent amongst these processes. Further research, experimental data and modelling intercomparisons are required to resolve some of these issues.     

Intercomparison of INAA and ICP-MS results for thorium determination in Pakistani diet

A pilot study on ingestion and organ content of trace elements of importance in radiological protection was to be carried out in Pakistan. Baseline analytical data on daily dietary intake of thorium was to be measured using Instrumental Neutron Activation Analysis (INAA) technique. To determine the accuracy and reliability of our technique, some samples were measured in Pakistan using INAA and in Japan using Inductively Coupled Plasma-Mass Spectrometry. For intercomparison of results overall mean Z-scores were calculated. The results showed validity of our technique. Mean value of 232Th concentration in Pakistani diet samples using INAA technique is 0.0062 +/- 0.0028 microg/g and with ICP-MS technique is 0.0069 +/- 0.0032 microg/g.     

Towards a non-animal risk assessment for anti-androgenic effects in humans

Toxicology testing is undergoing a transformation from a system based on high-dose studies in laboratory animals to one founded primarily on in vitro methods that evaluate changes in normal cellular signalling pathways using human-relevant cells or tissues. We review the tools and approaches that could be used to develop a non-animal safety assessment for anti-androgenic effects in humans, with a focus on the molecular initiating events (MIEs) that human disorders indicate critical for normal functioning of the hypothalamus–pituitary–testicular (HPT) axis. In vitro test systems exist which can be used to characterize the effects of test chemicals on some MIEs such as androgen receptor antagonism, inhibition of steroidogenic enzymes or 5α-reductase inhibition. When used alongside information describing the pharmacokinetics of a specific chemical exposure, these could be used to inform a pathways-based safety assessment. However, some parts of the HPT axis such as events occurring in the hypothalamus or pituitary are not well represented by accepted in vitro methods. In vitro tools to characterize perturbations in these events need to be developed before a fully integrated model of the HPT axis can be described. Knowledge gaps also exist which prevent us from using in vitro data to predict the type and severity of in vivo effect(s) that could arise from a given level of in vitro anti-androgenic activity. This means that more work is needed to reliably link an MIE with an adverse outcome. However, especially for chemicals with low anti-androgenic activity, human exposure data can be used to put in vitro mode of action data into context for risk-based safety decision-making.     

Determination of thorium, uranium and potassium elemental concentrations in surface soils in Cyprus

A comprehensive study was conducted to determine thorium, uranium and potassium elemental concentrations in surface soils throughout the accessible area of Cyprus using high-resolution gamma-ray spectrometry. A total of 115 soil samples was collected from all over the bedrock surface of the island based on the different lithological units of the study area. The soil samples were air-dried, sieved through a fine mesh, sealed in 1000-ml plastic Marinelli beakers, and measured in the laboratory in terms of their gamma radioactivity for a counting time of 18 h each. From the measured gamma-ray spectra, elemental concentrations were determined for thorium (range from 2.5 x 10(-3) to 9.8 microg g(-1)), uranium (from 8.1 x 10(-4) to 3.2 microg g(-1)) and potassium (from 1.3 x 10(-4) to 1.9%). The arithmetic mean values (A.M. +/- S.D.) calculated from all samples are: (1.2+/-1.7 microg g(-1)), (0.6+/-0.7) microg g(-1), and (0.4+/-0.3%), for thorium, uranium and potassium, respectively, which are by a factor of three-six lower than the world average values of 7.4 microg g(-1) (Th), 2.8 microg g(-1) (U) and 1.3% (K) derived from all data available worldwide. The best-fitting relation between the concentrations of Th and K versus U and also of K versus Th, is essentially of linear type with a correlation coefficient of 0.93, 0.84 and 0.90, respectively. The Th/U, K/U and K/Th ratios (slopes) extracted are equal to 2.0, 2.8 x 10(3) and 1.4 x 10(3), respectively.     

Seasonal changes in the spatial distribution of cellulolytic activity of soil microflora under conditions of atmospheric pollution

Spatial variation in the cellulolytic activity of the soil microflora during the growing season (from May to September) has been studied in spruce-fir forests exposed to emissions from the Middle Ural Copper-Smelting Plant. It has been shown that the average rate of decomposition of pure cellulose in polluted areas is significantly reduced, with its spatial variation being markedly increased. The spatial pattern of cellulolytic activity remains stable during the growing season, and the integrated parameters of frequency distributions in zones with different pollution levels change with time in the same direction.     

Distribution of persistent organic pollutants, polycyclic aromatic hydrocarbons and trace elements in soil and vegetation following a large scale landfill fire in northern Greece

Polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), including hexaclorocyclohexanes (HCHs) and DDTs, as well as trace elements were determined in soil and vegetation samples collected from the surrounding area of the landfill "Tagarades", the biggest in northern Greece, following a large scale fire involving approximately 50,000 tons of municipal waste. High concentrations of total PAHs, PCBs and heavy metals were found inside the landfill (1475 microg kg(-1) dw, 399 microg kg(-1) dw and 29.8 mg kg(-1) dw, respectively), whereas concentrations in the surrounding soils were by far lower ranging between 11.2-28.1 microg kg(-1) dw for PAHs, 4.02-11.2 microg kg(-1) dw for PCBs and 575-1207 mg kg(-1) dw for heavy metals. The distribution of HCHs and DDTs were quite different since certain soils exhibited equal or higher concentrations than the landfill. In vegetation, the concentrations of PAHs, PCBs, HCHs and DDTs ranged from 14.1-34.7, 3.64-25.9, 1.41-32.1 and 0.61-4.03 microg kg(-1) dw, respectively, while those of heavy metals from 81 to 159 mg kg(-1) dw. The results of the study indicated soil and vegetation pollution levels in the surroundings of the landfill comparable to those reported for other Greek locations. The impact from the landfill fire was not evident partially due to the presence of recent and past inputs from other activities (agriculture, vehicular transport, earlier landfill fires).     

Fate of HTO following its acute soil deposition at different growth stages of Chinese cabbage

Lysimeter experiments were carried out in a greenhouse to study the fate of HTO following its soil deposition at different growth stages of Chinese cabbage. An HTO solution was applied to the surface of an acidic sandy soil at a time before, and four different times after, sowing. The transfer of HTO to the plants was quantified with the areal transfer factor (TFa, m2 kg(-1)-fresh) defined as the ratio of the plant concentration at harvest to the areal activity deposition. In the four post-sowing applications, the TFa values were in the ranges of 1.6 x 10(-5)-4.9 x 10(-3) for TFWT and 4.5 x 10(-6) -4.3 x 10(-5) for OBT, increasing with a decrease in the time interval between application and harvest. In the pre-sowing application, which was followed by a soil mixing, the TFa values for TFWT and OBT were 1.3 x 10(-4) and 8.6 x 10(-6), respectively. One week after harvest, soil samplings were made for the applications at 26 (A(26)) and 63d (A(63)) after sowing. Peaks of the depth profiles of the soil HTO appeared in the 10-15 cm layer for A(26) and the 5-10 cm layer for A(63). The top 30 cm of soil contained 0.5% and 20% of the applied activity for A(26) and A(63), respectively. Negligible fractions seemed to be in the deeper zone. It was estimated that almost all or most of the applied HTO had escaped to the air before plants' harvest.     

Endocrine and metabolic changes in Anguilla anguilla L. following exposure to beta-naphthoflavone--a microsomal enzyme inducer

Anguilla anguilla L. were exposed during 24 and 48 h to 2.7 muM beta-naphthoflavone (BNF), a known microsomal enzyme inducer. The BNF effects on thyroid-stimulating hormone (TSH), free triiodothyronine (T3), free thyroxine (T4) and cortisol plasma levels were investigated. Alterations on plasma glucose and lactate levels were also measured as an indication of energy-mobilizing hormones alterations. BNF showed to be able to decrease significantly A. anguilla plasma T4 levels, whereas TSH, T3 and cortisol plasma remained constant. However, plasma glucose levels were significantly increased, demonstrating that intermediary metabolism has been affected. These results demonstrate that BNF a PAH-like compound alters the normal functioning of the hypothalamo-pituitary-thyroid (HPT) axis in A. anguilla.     

Biomonitoring of environmental pollution by thorium and uranium in selected regions of the Republic of Kazakhstan

Two former uranium mines and a uranium reprocessing factory in the city of Aktau, Kazakhstan, may represent a risk of contaminating the surrounding areas by uranium and its daughter elements. One of the possible fingerprinting tools for studying the environmental contamination is using plant samples, collected in the surroundings of this city in 2007 and 2008. The distribution pattern of environmental pollution by uranium and thorium was evaluated by determining the thorium and uranium concentrations in plant samples (Artemisia austriaca) from the city of Aktau and comparing these results with those obtained for the same species of plants from an unpolluted area (town of Kurchatov). The determination of the uranium and thorium concentrations in different parts of A. austriaca plants collected from the analyzed areas demonstrated that the main contamination of the flora in areas surrounding the city of Aktau was due to dust transported by the wind from the uranium mines. The results obtained demonstrate that all the areas surrounding Aktau have a higher pollution level due to thorium and uranium than the control area (Kurchatov). A few “hot points” with high concentrations of uranium and thorium were found near the uranium reprocessing factory and the uranium mines.     

Uranium and thorium in soils,mineral sands,water and food samples in a tin mining area in Nigeria with elevated activity

The activity concentrations of uranium and thorium have been determined in soils and mineral sands from the Nigerian tin mining area of Bisichi, located in the Jos Plateau, and from two control areas in Nigeria (Jos City and Akure) using high-purity germanium detectors (HPGe). High resolution sector field inductively coupled plasma mass spectroscopy (HR-SF-ICP-MS) was used to determine uranium and thorium in liquids and foodstuffs consumed locally in the mining area. The activities of uranium and thorium measured in the soils and mineral sands from Bisichi ranged from 8.7 kBq kg⁻¹ to 51 kBq kg⁻¹ for ²³⁸U and from 16.8 kBq kg⁻¹ to 98 kBq kg⁻¹ for ²³²Th, respectively. These values were significantly higher than those in the control areas of Jos City and Akure and than the reference values reported in the literature. They even exceeded the concentrations reported for areas of high natural radioactive background. Radionuclide concentrations in samples of the local foodstuffs and in water samples collected in Bisichi were found to be higher than UNSCEAR reference values. The results reveal the pollution potential of the mining activities on the surrounding areas.     

Increase of 210Po levels in human semen fluid after mussel ingestion

Polonium-210 (²¹⁰Po) radioactive concentrations were determined in human semen fluid of vasectomized non-smoker volunteers. The ²¹⁰Po levels ranged from 0.10 to 0.39 mBq g⁻¹ (mean: 0.23 ± 0.08 mBq g⁻¹). This value decreased to 0.10 ± 0.02 mBq g⁻¹ (range from 0.07 to 0.13 mBq g⁻¹) after two weeks of a controlled diet, excluding fish and seafood. Then, volunteers ate during a single meal 200 g of the cooked mussel Perna perna L., and ²¹⁰Po levels were determined again, during ten days, in semen fluid samples collected every morning. Volunteers continued with the controlled diet and maintained sexual abstinence through the period of the experiment. A 300% increase of ²¹⁰Po level was observed the day following mussel consumption, with a later reduction, such that the level returned to near baseline by day 4.     

Separation and measurement of thorium, plutonium, americium, uranium and strontium in environmental matrices

A technique for the isolation of thorium (Th), plutonium (Pu), americium (Am), uranium (U) and strontium (Sr) isotopes from various environmental matrices has been adapted from a previously published method specific to water samples (Maxwell, 2006). Separation and isolation of the various elemental fractions from a single sub-sample is possible, thereby eliminating the need for multiple analyses.The technique involves sample dissolution, concentration via calcium phosphate co-precipitation, rapid column extraction using TEVA™, TRU™ and Sr-Spec™ resin cartridges, alpha spectrometry for Th, Pu, U and Am and Cerenkov counting for Sr.Various standard reference materials were analysed and chemical yields are in the range of 70-80% for Th, Am, U and Sr and 50-60% for Pu. Sample sizes of up to 10 L for water, 5 g for dry soil and sediment and 10 g for dry vegetation and seaweed can be processed using this technique.     

Influence of plant activity and phosphates on thorium bioavailability in soils from Baotou area, Inner Mongolia

Harm of thorium to living organisms is governed by its bioavailability. Thorium bioavailability in the soil-plant system of Baotou rare earth industrial area was studied using pot experiments of wheat and single extraction methods. The effects of wheat growth stage and phosphate on thorium bioavailability were also investigated. Based on extractabilities of various extraction methods (CaCl₂, NH₄NO₃, EDTA, HOAc) and correlation analysis of thorium uptake by wheat plant and extractable thorium, a mixture of 0.02 M EDTA + 0.5 M NH₄OAc (pH 4.6) was found suitable for evaluation of thorium bioavailability in Baotou soil, which could be predicted quantitatively by multiple regression models. Because of differences of wheat root activities, thorium bioavailability in rhizosphere soil was higher than in bulk soil at tillering stage, but the reverse occurred at jointing stage. Phosphate addition induced the mineralization of soluble thorium by forming stable thorium phosphate compounds, and reduced thorium bioavailability in soil.     

A 10-year study of the 137Cs distribution in soil and a comparison of Cs soil inventory with precipitation-determined deposition

During a 10-year period, 1988-1998, surface soil samples have been collected at Blentarp in southern Sweden and analysed for 137Cs from the Chernobyl accident and from the nuclear weapons tests. The distance between the sampling plots on the different sampling occasions has been no more than 3 m. The results show that the depth distribution of 137Cs is very similar for each of the sampling occasions, indicating that the caesium migration at this site is very small. The total activity measured in the soil cores is in agreement with the calculated activity of 137Cs deposited at the site after nuclear weapons tests and the Chernobyl accident, based on air activity concentration and the amount of precipitation. The calculated deposition of 137Cs originating from the bomb tests amounts to 1.41 kBq m-2 for the period 1962-1986, which is in agreement with the activity of nuclear weapons fallout measured in the soil samples (1.60 kBq m-2 as a mean value of the first four years of sampling). The calculated activity of 137Cs of Chernobyl origin was 0.79 kBq m-2, which agrees well with the value of 0.79 kBq m-2 measured in the soil samples in 1988.