Bioavailability in soils

The consumption of locally-produced vegetables by humans may be an important exposure pathway for soil contaminants in many urban settings and for agricultural land use. Hence, prediction of metal and metalloid uptake by vegetables from contaminated soils is an important part of the Human Health Risk Assessment procedure. The behaviour of metals (cadmium, chromium, cobalt, copper, mercury, molybdenum, nickel, lead and zinc) and metalloids (arsenic, boron and selenium) in contaminated soils depends to a large extent on the intrinsic charge, valence and speciation of the contaminant ion, and soil properties such as pH, redox status and contents of clay and/or organic matter. However, chemistry and behaviour of the contaminant in soil alone cannot predict soil-to-plant transfer. Root uptake, root selectivity, ion interactions, rhizosphere processes, leaf uptake from the atmosphere, and plant partitioning are important processes that ultimately govern the accumulation ofmetals and metalloids in edible vegetable tissues. Mechanistic models to accurately describe all these processes have not yet been developed, let alone validated under field conditions. Hence, to estimate risks by vegetable consumption, empirical models have been used to correlate concentrations of metals and metalloids in contaminated soils, soil physico-chemical characteristics, and concentrations of elements in vegetable tissues. These models should only be used within the bounds of their calibration, and often need to be re-calibrated or validated using local soil and environmental conditions on a regional or site-specific basis.Mike J. McLaughlin, Erik Smolders, Fien Degryse, and Rene Rietr

Hepcidin and iron homeostasis during pregnancy.

Hepcidin is the master regulator of systemic iron bioavailability in humans. This review examines primary research articles that assessed hepcidin during pregnancy and postpartum and report its relationship to maternal and infant iron status and birth outcomes; areas for future research are also discussed. A systematic search of the databases Medline and Cumulative Index to Nursing and Allied Health returned 16 primary research articles including 10 human and six animal studies. Collectively, the results indicate that hepcidin is lower during pregnancy than in a non-pregnant state, presumably to ensure greater iron bioavailability to the mother and fetus. Pregnant women with undetectable serum hepcidin transferred a greater quantity of maternally ingested iron to their fetus compared to women with detectable hepcidin, indicating that maternal hepcidin in part determines the iron bioavailability to the fetus. However, inflammatory states, including preeclampsia, malaria infection, and obesity were associated with higher hepcidin during pregnancy compared to healthy controls, suggesting that maternal and fetal iron bioavailability could be compromised in such conditions. Future studies should examine the relative contribution of maternal versus fetal hepcidin to the control of placental iron transfer as well as optimizing maternal and fetal iron bioavailability in pregnancies complicated by inflammation

Validating the chronic Pb algae bioavailability model at high pH : single-species evaluation : final report, 12 June 2017

We investigated toxicity of Pb to Pseudokirchneriella subcapitata using the standard 72h-growth inhibition assays at 2 pH levels (pH 7.2 & pH 8.4) and 2 P (P 10 ug/L & P 100 ug/L) levels, i.e. at 4 treatments in total. This was done to test whether an existing algae Pb bioavailability model developed for pH≤8.0, can be used at higher pH>8.0. The algae Pb bioavailability model calibrated on Pb toxicity at pH 7.2 (P 100 µg/L) predicted filtered Pb toxicity(EC50 and EC20) at pH 8.4 (P 100 µg/L) with reasonable accuracy, i.e. within 2-fold error. Although the slope of the linear relationship between pH and log10(EC50 as Pb2+ acitivity) for the pH range between 7.2 and 8.4 (present study) was slightly lower than that of the pH range between 6 and 8 (existing model), our study suggests that the chronic algae Pb bioavailability model can be extrapolated to predict Pb toxicity up to pH 8.4

Zinc accumulation and utilisation by wine yeasts

The present study has focused on the accumulation of zinc by wine yeast strains of Saccharomyces cerevisiae during fermentation of both grape juice and chemically defined medium with different carbohydrates and at varying levels of zinc. The results have shown that zinc accumulation by wine yeast was very rapid with all zinc being removed from the medium by yeast cells within the first two hours. Zinc uptake was stimulated by the presence of sucrose. Zinc affected fermentation progress at defined levels, with optimal concentrations at 1.5–2.5 ppm, depending on yeast strain and zinc bioavailability. The bioavailability of metal ions in grape must and the roles of metals in wine yeast physiology are aspects poorly understood by enologists. In brewing, it has long been recognized that malt wort may be zinc deficient and brewers often carry out zinc supplementations to avoid sluggish and incomplete fermentations. In winemaking, zinc levels in grape musts may be compromised depending on the bioavailability of zinc ions in vineyard soils as well as treatments with fertilizers and fungicides during grape growing. As a consequence, sub-optimal zinc levels in grape musts may negatively influence the fermentative performance of yeasts. We believe that optimization of metal ion bioavailability will improve yeast fermentation performance in industrial processes and this study addresses some issues relating to zinc in enology

Folate bioavailability

An inadequate folate status is associated with increased risk of anaemia and neural tube defects. In many countries a folate intake below recommendations has been reported for women in childbearing age. However, data on folate intake and status are not always associated, since factors other than intake, e.g. bioavailability, affect folate status. This thesis studied the bioavailability of folate using in vivo and in vitro models. The effect of two pieces of Swedish nutritional advice on folate status of healthy women was assessed in a 12-week randomised controlled intervention trial. By combining a human plasma area under the curve (AUC)/ileostomy model with a stable isotope technique, the bioavailability of wholemeal bread fortified with reduced folate (5-CH3-H4folate) or folic acid was determined. In vitro effects of the food matrix on bioaccessibility and uptake of reduced folates were studied using a dynamic gastrointestinal model (TIM) and Caco-2 cells. The intervention breakfast diet (contributing ~1/3 of recommended daily folate intake) significantly improved folate status of the women, indicating a high folate bioavailability. The bread intervention diet (contributing ~1/5 of recommended daily folate intake) maintained folate and decreased homocysteine concentrations. Based on folate content in stomal effluent, the bioavailability of both folate fortificants tested was similarly high (~90%) but plasma kinetics differed significantly depending on ingested folate form. Data from in vitro TIM and Caco-2 cell experiments showed an inhibitory effect (~25%) of the bread matrix on bioaccessibility and uptake of reduced folates, which was higher than in vivo findings. Overall, data from these in vivo and in vitro studies suggest that the bioavailability of reduced folate is high and comparable to that of synthetic folic acid. Food matrix effects, e.g. of bread or a typical breakfast meal, on folate bioavailability seem negligible at physiological folate intake doses

Bioavailability of pesticides in freshwater sediments

In ecological risk assessment standardized sediment toxicity tests are used to predict the hazard of chemicals for sediment-living organisms. Feeding is a prerequisite in these long-term tests to avoid starvation of test organisms. Therefore, added food particles may act as vectors for the test compound. The importance of food particles as vectors, however, is dependent on several factors, for example, sorption and major uptake routes. In this thesis, laboratory experiments on the importance of pesticide sorption and uptake routes for the bioavailability to the midge Chironomus riparius in sediment toxicity test setups were performed. A feeding selectivity study showed that larvae almost exclusively fed on added food particles, and highly neglected sediment particles. Additionally, experiments on the sorption of the insecticide lindane, showed that food and peat particles (used in artificial sediment) efficiently sorbed lindane (>95% after 48 h). The binding strength of lindane was weak, facilitating particulate uptake. However, the uptake from dissolved lindane was higher than the uptake from particles. From this we concluded that toxicity may be underestimated in spiked-sediment scenarios, where hydrophobic pesticides sorb to the sediment and larvae to a large extent feed on uncontaminated food particles. Conversely, in a spiked-water scenario, the food particles may act as vector, resulting in a facilitated particulate uptake, in addition to the uptake from water. Sediment organic matter affects sorption, and thus bioavailability of pesticides. Pyrethroid toxicity was much higher in artificial sediment than in a natural sediment, indicating the simplicity and shortcomings of using artificial sediments. Interestingly, the sediment quality highly affected bioavailability in spiked-water. For example, C. riparus larvae in sediments with low organic matter content and exposed to spiked-water pyrethroids, showed lower survival, slower development, and increased adult size, than those in sediments with higher organic matter. The pyrethroid deltamethrin, showed an LC50-value (28 d) for C. riparius larvae in artificial sediment of 16 pg/L and 11 µg/kg for water- and sediment exposures, respectively, i.e. toxic effects occurred at concentrations lower than the detection limits for high-tech analytical methods. This thesis contributes to a wider understanding of processes affecting bioavailability in freshwater sediments, and in particular in standardized sediments used in toxicity testing. The understanding of test compound sorption and bioavailability is crucial for sound interpretations of toxicity tests and for the general credibility of such tests

Genetic programming in data mining for drug discovery

Genetic programming (GP) is used to extract from rat oral bioavailability (OB) measurements simple, interpretable and predictive QSAR models which both generalise to rats and to marketed drugs in humans. Receiver Operating Characteristics (ROC) curves for the binary classier produced by machine learning show no statistical dierence between rats (albeit without known clearance dierences) and man. Thus evolutionary computing oers the prospect of in silico ADME screening, e.g. for \virtual" chemicals, for pharmaceutical drug discovery

The in vitro assessment of the bioavailability of iron in New Zealand beef : a thesis presented in partial fulfillment of the requirements for the degree of Master of Science in Physiology at Massey University, Palmerston North, New Zealand /

The bioavailability of iron in New Zealand beef either alone or as part of a 'typical' New Zealand meal was investigated. The solubility of iron and its in vitro absorption by mouse intestinal tissue were used to evaluate iron bioavailability. The solubility of haem and/or non-haem iron in meat (beef longissimus muscle), vegetables and meat-plus-vegetables was investigated. Samples were cooked and then subjected to in vitro gastrointestinal digestion with pepsin followed by a combination of pancreatic enzymes and bile. Cooking at 65°C for 90 minutes reduced the soluble iron concentration in meat by 81% and reduced the haem iron concentration by 27%, which coincided with a 175% increase in non-haem iron concentrations. However, gastrointestinal digestion increased the solubility of iron in cooked meat (333%), vegetables (367%) and meat-plus-vegetables (167%). A proportion (35%) of the haem iron in the meat was broken down by the action of pancreatic enzymes leading to a 46% increase in non-haem iron concentrations, although this was not the case for the meat-plus-vegetables. Validation studies showed that mouse intestinal segments mounted in Ussing chambers maintained integrity and viability, and were responsive to glucose, theophylline and carbachol. Intestinal tissue from iron deficient mice was then used in the Ussing chambers to investigate the absorption of iron from ferrous gluconate and the soluble fractions of meat, vegetables and meat-plus-vegetables after gastrointestinal digestion. Results indicated a trend towards a higher absorption of iron from meat and ferrous gluconate, compared to vegetables and meat-plus-vegetables. However, iron absorption results were difficult to interpret due to the wide variation in the data. This variation was possibly due to errors associated with the sample processing and the analysis of iron, which was by inductively coupled-mass spectroscopy. Overall, the present study showed that before estimations can be made on the bioavailability of food iron, the effects of the cooking and gastrointestinal digestion processes must be considered. Further, the use of in vitro gastrointestinal digestion followed by the use of Ussing chambers to assess intestinal absorption is a potentially valuable system for assessing mineral bioavailability

Use of isotope dilution method to predict bioavailability of organic pollutants in historically contaminated sediments.

Many cases of severe environmental contamination arise from historical episodes, where recalcitrant contaminants have resided in the environment for a prolonged time, leading to potentially decreased bioavailability. Use of bioavailable concentrations over bulk chemical levels improves risk assessment and may play a critical role in determining the need for remediation or assessing the effectiveness of risk mitigation operations. In this study, we applied the principle of isotope dilution to quantify bioaccessibility of legacy contaminants DDT and PCBs in marine sediments from a Superfund site. After addition of 13C or deuterated analogues to a sediment sample, the isotope dilution reached a steady state within 24 h of mixing. At the steady state, the accessible fraction (E) derived by the isotope dilution method (IDM) ranged from 0.28 to 0.89 and was substantially smaller than 1 for most compounds, indicating reduced availability of the extensively aged residues. A strong linear relationship (R2=0.86) was found between E and the sum of rapid (Fr) and slow (Fs) desorption fractions determined by sequential Tenax desorption. The IDM-derived accessible concentration (Ce) was further shown to correlate closely with tissue residue in the marine benthic polychaete Neanthes arenaceodentata exposed in the same sediments. As shown in this study, the IDM approach involves only a few simple steps and may be readily adopted in laboratories equipped with mass spectrometers. This novel method is expected to be especially useful for historically contaminated sediments or soils, for which contaminant bioavailability may have changed significantly due to aging and other sequestration processes

Metabolic profile, bioavailability and toxicokinetics of zearalenone-14-glucoside in rats after oral and intravenous administration by liquid chromatography high-resolution mass spectrometry and tandem mass spectrometry

Zearalenone-14-glucoside (ZEN-14G), a key modified mycotoxin, has attracted a great deal of attention due to the possible conversion to its free form of zearalenone (ZEN) exerting toxicity. In this study, the toxicokinetics of ZEN-14G were investigated in rats after oral and intravenous administration. The plasma concentrations of ZEN-14G and its major five metabolites were quantified using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The data were analyzed via non-compartmental analysis using software WinNonlin 6.3. The results indicated that ZEN-14G was rapidly hydrolyzed into ZEN in vivo. In addition, the major parameters of ZEN-14G following intravenous administration were: area under the plasma concentration-time curve (AUC), 1.80 h.ng/mL; the apparent volume of distribution (V-Z), 7.25 L/kg; and total body clearance (CL), 5.02 mL/h/kg, respectively. After oral administration, the typical parameters were: AUC, 0.16 h.ng/mL; V-Z, 6.24 mL/kg; and CL, 4.50 mL/h/kg, respectively. The absolute oral bioavailability of ZEN-14G in rats was about 9%, since low levels of ZEN-14G were detected in plasma, which might be attributed to its extensive metabolism. Therefore, liquid chromatography high-resolution mass spectrometry (LC-HRMS) was adopted to clarify the metabolic profile of ZEN-14G in rats' plasma. As a result, eight metabolites were identified in which ZEN-14-glucuronic acid (ZEN-14GlcA) had a large yield from the first time-point and continued accumulating after oral administration, indicating that ZEN-14-glucuronic acid could serve a potential biomarker of ZEN-14G. The obtained outcomes would prompt the accurate safety evaluation of ZEN-14G