Review: Bioavailability of trace elements in farm animals: definition and practical considerations for improved assessment of efficacy and safety.

Currently, the authorisation procedure of trace elements as feed additives in the European Union according to Regulation (EC) No. 1831/2003 does not consider the bioavailability of trace element sources. This manuscript provides framework conditions for in vivo experiments that aim to estimate differences in the relative bioavailability between supplements of essential trace elements. Framework conditions encompass necessary technical information on the test substance, the experimental design and diet composition as well as the suitability of status parameters that allow for relative comparisons of regression variables. This manuscript evolves recommendations for researchers to conduct solid and reliable experiments on the matter as well as decision makers to interpret the value of studies submitted with authorisation applications regarding a certain trace element supplement.

Reference values of trace elements in blood and/or plasma in adults living in Belgium.

OBJECTIVES: Trace elements (TEs) from natural and anthropogenic sources are ubiquitous. Essential or not, their relevance for human health and disease is constantly expanding. Biological monitoring is a widely integrated tool in risk assessment both in occupational and environmental settings. However, the determination of appropriate and accurate reference values in the (specific) population is a prerequisite for a correct interpretation of biomonitoring data. This study aimed at determining the reference distribution for TEs (Al, As, Sb, Be, Bi, Cd, Co, Cu, Mn, Hg, Mo, Ni, Pb, Se, Tl, Sn, V, Zn) in the blood and/or plasma of the adult population in Belgium. METHODS: Blood and plasma samples were analyzed for 178 males and 202 females, recruited according to an a priori selection procedure, by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Reference values were established with high confidence for AsT, Cd, Cu, HgT, Mn, Mo, Pb, Sn, Se, Tl and Zn. Compared to previously published data in the Belgian population, a decreasing time trend is observed for Zn, Cd and Pb. Globally, the results also indicate that the current exposure levels to TEs in the Belgian population are similar to those from other recent national surveys. CONCLUSIONS: These reference values and limits obtained through validated analytical and statistical methods will be useful for future occupational and/or environmental surveys. They will contribute to decision-making concerning both public health policies but also exposure assessments on an individual scale.

Development and characterization of reference materials for trace element analysis of keratinized matrices.

Biomonitoring for human exposure to lead, arsenic, mercury, and other toxic metal(loid)s often relies on analyzing traditional biospecimens such as blood and urine. While biomonitoring based on blood and urine is well-established, non-traditional biospecimens such as hair and nails can offer the potential to explore past exposures as well as the advantages of non-invasive collection and ease of storage. The present study describes the production of four reference materials (NYS RMs 18-01 through 18-04) based on caprine horn, a keratinized tissue similar to human hair and nails, intended to serve as a resource for calibration, quality control, and method validation purposes. The elemental content and homogeneity of these candidate reference materials were characterized for 17 elements using inductively coupled plasma mass spectrometry (ICP-MS). Commutability between two or more of the NYS caprine horn RMs and human nails was established for 8 elements (Ba, Ca, Cr, Cu, Mn, Pb, Sr, and Zn) based on analysis by ICP-MS/MS and ICP-optical emission spectrometry. The development and optimization of an ICP-MS/MS instrumental method for the determination of 17 elements in keratinized tissues is described. The method was validated against three certified reference materials based on human hair showing good accuracy and method repeatability better than 25% for all analytes. This study also describes sample preparation issues and addresses common challenges including surface contamination, microwave digestion, matrix effects, and spectral interferences in inorganic mass spectrometry. New York State Department of Health Keratin Matrix Reference Materials. Graphical abstract.

The Reference Values of Hair Content of Trace Elements in Dairy Cows of Holstein Breed.

The objective of this study was to assess trace element content in hair of Holstein dairy cows bred in the Leningrad Region of Russia and to calculate the site-specific reference intervals. Hair content of arsenic, boron, cadmium, cobalt, chromium, copper, iron, mercury, iodine, lithium, manganese, lead, selenium, silicon, tin, strontium, vanadium, and zinc in 148 cows during first (n = 50), second (n = 48), and third (n = 50) lactation periods of life was determined using inductively coupled plasma mass spectrometry. Dietary intake of trace elements corresponded to the adequate values according to national and international recommendations. Comparative analysis did not reveal any significant differences in hair content of main essential elements on the animals depending on the number of lactation. At the same time, the first-lactation cows had significantly (P < 0.05) lower concentration of lead in hair as compared to the third-lactation cows and a higher level of mercury as compared to the second-lactation cows. The reference intervals and 90% confidence intervals for the lower and upper limits were calculated in agreement with the American Society for Veterinary Clinical Pathology Quality Assurance and Laboratory Standard Guidelines.

Calibration strategies for elemental analysis of biological samples by LA-ICP-MS and LIBS - A review.

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and laser-induced breakdown spectroscopy (LIBS) are widely accepted techniques for direct sampling of biological materials for elemental analysis, with increasing applications being reported over the recent years. This review is focused on the calibration materials used to quantify trace elements in different biological samples such as soft tissues (for instance brain, liver, hair) and hard tissues (bones and teeth). The design of a correct calibration strategy relies on the choice of an adapted reference material that can be commercially available or prepared in-house, which will be reviewed here. A large variety of methods has been approached and considered promising over the years, and the development of matrix-matched reference biological materials seems now closer than ever and gives hope to even better quantitation using LIBS and LA-ICP-MS.

Establishing baseline trace metals in marine bivalves in China and worldwide: Meta-analysis and modeling approach.

Bivalves are extensively employed as biomonitors of coastal pollution, but the comparability among different species and geographic environments needs to be further scrutinized. The present study conducted a meta-analysis of trace metals (Ag, Cd, Cr, Cu, Ni, Pb, Ti, and Zn) in the soft tissues of three groups of marine bivalves (oysters, mussels, and clams) collected from China and worldwide. By conducting cumulative frequency distribution analysis of metal distribution, we modeled the 5% cumulative values as the bio-baseline metal concentrations in these bivalves. We further modeled their potential baseline concentrations using a well-developed biokinetic model. The baseline concentrations of Cd, Cu, and Zn in the tissue-specific Environmental Quality Standards (EQSs) for China were 0.99, 34.5, and 340 µg/g dw in oysters, 0.38, 4.32, and 49.6 µg/g dw in mussels, and 0.35, 3.02, 51.4 µg/g dw in clams, respectively. Of the 8 metals examined in this study, the calculated baseline concentrations of Ag, Cr, Cd, Cu and Zn in the oysters were 3.7-48, 2.7-3.6, 2.6-2.8, 8.0-11.4, 6.6-6.8 times higher than those in the mussels and clams, and only Ti showed comparable baseline concentrations among the three bivalves (8.43-9.67 µg/g dw). These data strongly suggested the inter-group as well as inter-metal difference in the baseline metal concentrations in marine bivalves. Further, the potential baseline concentrations of Cd and Cu predicted by the biokinetic model were comparable to those modeled by the probability frequency distribution. Combined statistical frequency analysis and biokinetic modeling therefore provided an innovative method to establish the baseline metal concentrations in bivalves and the tissue-specific EQSs, which are now urgently needed for coastal management, biomonitoring, and geochemical records in the world.

Assessment of water quality and trace metal contaminations in Mondolkiri province in the Northeastern part of Cambodia.

The aim of the present study is to investigate water quality and potential trace metal contaminations in the Northeastern part of Cambodia. Tube well (n = 35), hand-dug well (n = 18), channel (n = 10) and lake/pond (n = 8) water samples were randomly collected from Mondolkiri province which is located in the Northeastern highland of Cambodia. A water sample was collected in two different bottles. One was filled in 30-mL polyethylene bottle after which was acidified to pH < 2 with concentrated HNO3. Another was filled in 250-mL polyethylene bottle. The collected water sampled was stored in a cooler during fieldwork and transferred to a fridge where they are stored at 4 °C for analysis. The measurement of pH, ORP, dissolved oxygen (DO), turbidity, conductivity, total dissolved solids (TDS) and salinity was taken at laboratory following standard procedures. All chemical measurement of trace metals were taken by inductively coupled plasma mass spectrometry (ICP-MS). Analytical results reveal that tube well (47.1%), hand-dug well (77.8%) and channel water (20%) have pH < 6.5. Turbidity of tube well (32.4%), hand-dug well (5.6%), lake water (12.5%) and all channel water samples are exceeded Cambodia regulation of 5 NTU. Mean As, Cd, Cr, Cu, Ni, Pb and Zn concentrations in Mondolkiri's water sources are below Cambodian drinking water quality standard and WHO's drinking water quality guideline. However, the upper range of Pb in tube well and channel water and Zn in tube well are exceeding Cambodia regulation. Concurrently, the mean concentrations of Fe and Mn in tube well and channel water are exceeded Cambodian aesthetic guideline of 300 µg L-1 and 100 µg L-1, respectively. This study suggests that appropriate treatment technologies are necessary for residents in the Mondolkiri province to access to clean water and minimize their potential health risks.

Nutritionally recommended food for semi- to strict vegetarian diets based on large-scale nutrient composition data.

Diet design for vegetarian health is challenging due to the limited food repertoire of vegetarians. This challenge can be partially overcome by quantitative, data-driven approaches that utilise massive nutritional information collected for many different foods. Based on large-scale data of foods' nutrient compositions, the recent concept of nutritional fitness helps quantify a nutrient balance within each food with regard to satisfying daily nutritional requirements. Nutritional fitness offers prioritisation of recommended foods using the foods' occurrence in nutritionally adequate food combinations. Here, we systematically identify nutritionally recommendable foods for semi- to strict vegetarian diets through the computation of nutritional fitness. Along with commonly recommendable foods across different diets, our analysis reveals favourable foods specific to each diet, such as immature lima beans for a vegan diet as an amino acid and choline source, and mushrooms for ovo-lacto vegetarian and vegan diets as a vitamin D source. Furthermore, we find that selenium and other essential micronutrients can be subject to deficiency in plant-based diets, and suggest nutritionally-desirable dietary patterns. We extend our analysis to two hypothetical scenarios of highly personalised, plant-based methionine-restricted diets. Our nutrient-profiling approach may provide a useful guide for designing different types of personalised vegetarian diets.

A nested multivariate chemometrics based calibration strategy for direct trace biometal analysis in soft tissue utilizing Energy Dispersive X-Ray Fluorescence (EDXRF) and scattering spectrometry.

Compton scatter-modulated fluorescence and multivariate chemometric (artificial neural network (ANN) and principal component regression (PCR)) calibration strategy was explored for direct rapid trace biometals (Mn, Fe, Cu, Zn, Se) analysis in "complex" matrices (model soft tissues). This involved spectral feature selection (multiple fluorescence signatures) normalized to or in conjunction with Compton scatter. ANN model resulted in more accurate trace biometal determination (R2>0.9) compared to PCR. Hybrid nested (ANN and PCR) approach led to optimized accurate biometals' concentrations in Oyster tissue (≤ ± 10%).

Development of a Certified Reference Material (NMIJ CRM 7203-a) for Elemental Analysis of Tap Water.

A certified reference material (CRM), NMIJ CRM 7203-a, was developed for the elemental analysis of tap water. At least two independent analytical methods were applied to characterize the certified value of each element. The elements certified in the present CRM were as follows: Al, As, B, Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Mo, Na, Ni, Pb, Rb, Sb, Se, Sr, and Zn. The certified value for each element was given as the (property value ± expanded uncertainty), with a coverage factor of 2 for the expanded uncertainty. The expanded uncertainties were estimated while considering the contribution of the analytical methods, the method-to-method variance, the sample homogeneity, the long-term stability, and the concentrations of the standard solutions for calibration. The concentration of Hg (0.39 µg kg-1) was given as the information value, since loss of Hg was observed when the sample was stored at room temperature and exposed to light. The certified values of selected elements were confirmed by a co-analysis carried out independently by the NMIJ (Japan) and the KRISS (Korea).

High Precision Zinc Stable Isotope Measurement of Certified Biological Reference Materials Using the Double Spike Technique and Multiple Collector-ICP-MS.

Biological reference materials with well-characterised stable isotope compositions are lacking in the field of 'isotope biochemistry', which seeks to understand bodily processes that rely on essential metals by determining metal stable isotope ratios. Here, we present Zn stable isotope data for six biological reference materials with certified trace metal concentrations: fish muscle, bovine muscle, pig kidney, human hair, human blood serum and human urine. Replicate analyses of multiple aliquots of each material achieved reproducibilities (2sd) of 0.04-0.13‰ for δ66/64Zn (which denotes the deviation of the 66Zn/64Zn ratio of a sample from a pure Zn reference material in parts per 1000). This implies only very minor isotopic heterogeneities within the samples, rendering them suitable as quality control materials for Zn isotope analyses. This endorsement is reinforced by (i) the close agreement of our Zn isotope data for two of the samples (bovine muscle and human blood serum) to previously published results for different batches of the same material and (ii) the similarity of the isotopic data for the samples (δ66/64Zn ≈ -0.8 to 0.0‰) to previously published Zn isotope results for similar biological materials. Further tests revealed that the applied Zn separation procedure is sufficiently effective to enable accurate data acquisition even at low mass resolving power (M/ΔM ≈ 400), as measurements and analyses conducted at much higher mass resolution (M/ΔM ≈ 8500) delivered essentially identical results.

Analysis of whole human blood for Pb, Cd, Hg, Se, and Mn by ICP-DRC-MS for biomonitoring and acute exposures.

We improved our inductively coupled plasma mass spectrometry (ICP-MS) whole blood method [1] for determination of lead (Pb), cadmium (Cd), and mercury (Hg) by including manganese (Mn) and selenium (Se), and expanding the calibration range of all analytes. The method is validated on a PerkinElmer (PE) ELAN® DRC II ICP-MS (ICP-DRC-MS) and uses the Dynamic Reaction Cell (DRC) technology to attenuate interfering background ion signals via ion-molecule reactions. Methane gas (CH4) eliminates background signal from 40Ar2+ to permit determination of 80Se+, and oxygen gas (O2) eliminates several polyatomic interferences (e.g. 40Ar15N+, 54Fe1H+) on 55Mn+. Hg sensitivity in DRC mode is a factor of two higher than vented mode when measured under the same DRC conditions as Mn due to collisional focusing of the ion beam. To compensate for the expanded method's longer analysis time (due to DRC mode pause delays), we implemented an SC4-FAST autosampler (ESI Scientific, Omaha, NE), which vacuum loads the sample onto a loop, to keep the sample-to-sample measurement time to less than 5min, allowing for preparation and analysis of 60 samples in an 8-h work shift. The longer analysis time also resulted in faster breakdown of the hydrocarbon oil in the interface roughing pump. The replacement of the standard roughing pump with a pump using a fluorinated lubricant, Fomblin®, extended the time between pump maintenance. We optimized the diluent and rinse solution components to reduce carryover from high concentration samples and prevent the formation of precipitates. We performed a robust calculation to determine the following limits of detection (LOD) in whole blood: 0.07µgdL-1 for Pb, 0.10µgL-1 for Cd, 0.28µgL-1 for Hg, 0.99µgL-1 for Mn, and 24.5µgL-1 for Se.

Stability of Vitamin A, Iron and Zinc in Fortified Rice during Storage and Its Impact on Future National Standards and Programs--Case Study in Cambodia.

Fortified rice holds great potential for bringing essential micronutrients to a large part of the world population. The present study quantified the losses of three different micronutrients (vitamin A, iron, zinc) in fortified rice that were produced using three different techniques (hot extrusion, cold extrusion, and coating) and stored at two different environments (25 ± 5 °C at a humidity of 60% and 40 ± 5 °C at a humidity of 75%) for up to one year. Fortified rice premix from the different techniques was mixed with normal rice in a 1:100 ratio. Each sample was analyzed in triplicate. The study confirmed the high stability of iron and zinc during storage while the retention of vitamin A was significantly affected by storage and the type of techniques used to make rice premix. Losses for iron and zinc were typically <10% for any type of rice premix. After 12 months at mild conditions (25 °C and humidity of 60%), losses for vitamin A ranged from 20% for cold extrusion, 30% for hot extruded rice 77% for coated rice premix. At higher temperatures and humidity, losses of vitamin A were 40%-50% for extruded premix and 93% for coated premix after 6 months. We conclude that storage does lead to a major loss of vitamin A and question whether rice is a suitable food vehicle to fortify with vitamin A. For Cambodia, fortification of rice with iron and zinc could be an effective strategy to improve the micronutrient status of the population if no other food vehicles are available.

A Call to Action to Bring Safer Parenteral Micronutrient Products to the U.S. Market.

The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) started an intensive review of commercially available parenteral vitamin and trace element (TE) products in 2009. The chief findings were that adult multi-TE products currently available in the United States (U.S.) provide potentially toxic amounts of manganese, copper, and chromium, and neonatal/pediatric multi-TE products provide potentially toxic amounts of manganese and chromium. The multivitamin products appeared safe and effective; however, a separate parenteral vitamin D product is needed for those patients on standard therapy who continue to be vitamin D depleted and are unresponsive to oral supplements. The review process also extended to parenteral choline and carnitine. Although choline and carnitine are not technically vitamins or trace elements, choline is an essential nutrient in all age groups, and carnitine is an essential nutrient in infants, according to the Food and Nutrition Board of the Institute of Medicine. A parenteral choline product needs to be developed and available. Efforts are currently under way to engage the U.S. Food and Drug Administration (FDA) and the parenteral nutrient industry so A.S.P.E.N.'s recommendations can become a commercial reality.

Dietary intake of trace elements by the population of Catalonia (Spain): results from a total diet study.

This study aimed to analyse the concentrations of Al, Ba, Bi, Cu, Cr, Ge, Mn, Mo, Ni, Sb, Se, Sr and Zn in food samples collected in 2008 in Catalonia (Spain). The dietary intake of these 13 trace elements was subsequently estimated by different age-gender groups of the population: children, adolescents, adults and seniors. In general terms, fish and shellfish, cereals, and pulses were the food groups showing the highest levels for most elements. Higher dietary intakes were associated with male groups (adolescents, adults and seniors). However, none exceeded the tolerable levels. When exposure was estimated based on body weight, children were the group with the highest dietary intake. Notwithstanding, only the weekly intake of Al by children exceeded the recommendations of the European Food Safety Authority (EFSA). It is a consequence of the higher intake of cereals in relation to their respective body weights. In addition to the periodical food surveillance of toxic metals (As, Cd, Hg and Pb), it is also important to determine the levels of other trace elements in order to ensure that the dietary exposure by the Catalan population is under control.

Review of trace mineral requirements for preterm infants: what are the current recommendations for clinical practice?

Inadequate nutrient stores at birth are an inevitable consequence of being born prematurely. Preterm infants also have high nutrient requirements, which increase with earlier gestational ages. As a result, early nutrition intervention is required to prevent further deficits that, if not corrected, can affect growth and long-term outcomes. Preterm infants often require several weeks of parenteral nutrition (PN) support, which includes trace mineral supplementation. Trace minerals are considered essential nutrients, unable to be synthesized in the human body. Deficiencies of trace minerals have been reported, yet evidence-based guidelines for assessment and supplementation have not been clearly defined. Food and Drug Administration-approved parenteral trace mineral intake guidelines are more than 30 years old. In an effort to more clearly define trace mineral supplementation and monitoring guidelines for preterm infants, a review of literature was performed with the purpose to (1) summarize trace mineral roles in preterm infants, (2) describe clinical signs of deficiency and toxicity, and (3) present intake recommendations and considerations for preterm infants based on current available literature. Review of literature was completed using PubMed and Cochrane databases to find relevant studies specific to trace mineral requirements for preterm infants, trace mineral supplementation of PN, human milk fortifiers, and preterm infant formulas. Review of literature supports that trace mineral depletion can lead to clinical compromise in preterm infants; therefore, suggesting that every effort be made to ensure adequate provision of trace minerals is given to preterm infants. Practical considerations for the clinical nutrition management of preterm infants were also identified in this review.

Background concentrations and reference values for heavy metals in soils of Cuba.

The potential threat of heavy metals to human health has led to many studies on permissible levels of these elements in soils. The objective of this study was to establish quality reference values (QRVs) for Cd, Pb, Zn, Cu, Ni, Cr, Fe, Mn, As, Hg, V, Ba, Sb, Ag, Co, and Mo in soils of Cuba. Geochemical associations between trace elements and Fe were also studied, aiming to provide an index for establishing background concentrations of metals in soils. Surface samples of 33 soil profiles from areas of native forest or minimal anthropic influence were collected. Samples were digested (USEPA method 3051A), and the metals were determined by ICP-OES. The natural concentrations of metals in soils of Cuba followed the order Fe > Mn > Ni > Cr > Ba > V > Zn > Cu > Pb > Co > As > Sb > Ag > Cd > Mo > Hg. The QRVs found for Cuban soils were as follows (mg kg(-1)): Ag (1), Ba (111), Cd (0.6), Co (25), Cr (153), Cu (83), Fe (54,055), Mn (1947), Ni (170), Pb (50), Sb (6), V (137), Zn (86), Mo (0.1), As (19), and Hg (0.1). The average natural levels of heavy metals are above the global average, especially for Ni and Cr. The chemical fractionation of soil samples presenting anomalous concentrations of metals showed that Cu, Ni, Cr, Sb, and As have low bioavailability. This suggests that the risk of contamination of agricultural products via plant uptake is low. However, the final decision on the establishment of soil QRVs in Cuba depends on political, economic, and social issues and in-depth risk analyses considering all routes of exposure to these elements.

Multivitamins/multiminerals in Switzerland: not as good as it seems.

BACKGROUND: Multivitamin/multimineral (MVM) supplements are commonly consumed by the general population, but little is known regarding their composition and compliance with local regulations. We assessed the composition and compliance with regulations [no indication in the label of vitamin/minerals amounting <15% of the acceptable daily intake (ADI)] of MVM available in Switzerland. METHODS: The composition of vitamin/minerals supplements was obtained from the Swiss drug compendium, the Internet, pharmacies, parapharmacies and supermarkets. MVM was defined as the presence of at least 5 vitamins and/or minerals. RESULTS: Of the 254 vitamin/mineral supplements collected, 95 (37%) were considered as MVM. The most frequent vitamins were B6 (73.7%), C (71.6%), B2 (69.5%) and B1 (67.4%); the least frequent were K (17.9%), biotin (51.6%), pantothene (55.8%) and E (56.8%). Approximately half of MVMs provided >150% of the ADI for vitamins. The most frequent minerals were zinc (66.3%), calcium (55.8%), magnesium (54.7%) and copper (48.4%), and the least frequent were fluoride (3.2%), phosphorous (17.9%), chrome (22.1%) and iodine (25%). More than two thirds of MVMs provided between 50 and 150% of the ADI for minerals, and few MVMs provided >150% of the ADI. While few MVMs provided <15% of the ADI for vitamins, a considerable fraction did so for minerals (32.7% for magnesium, 26.1% for copper and 22.6% for calcium). CONCLUSION: There is a great variability regarding the composition of MVMs available in Switzerland. Several MVM do not comply with Swiss regulations, which calls for monitoring and corrective measures.

Reference values and upper reference limits for 26 trace elements in the urine of adults living in Belgium.

BACKGROUND: Trace elements (TEs) are ubiquitous and their potential interest for human health has been constantly expanding. Biological monitoring is generally considered to be a useful tool to assess human exposure to chemical agents in risk assessment both at occupational and environmental levels. However, the knowledge of accurate reference values, which may vary across countries or regions, is a prerequisite for correct interpretation of biomonitoring data. This study aimed at determining the reference distribution and the upper reference limit for 26 TEs (Al, As, Sb, Ba, Be, Bi, Cd, Cr, Co, Cu, In, Li, Mn, Hg, Mo, Ni, Pd, Pt, Pb, Se, Te, Tl, Sn, U, V, Zn) in the urine of the general adult population residing in Belgium. METHODS: In total, 1022 adults not occupationally or extra-occupationally (mainly via hobbies, drugs) exposed to these TEs were recruited by occupational physicians and toxicologists according to an a priori selection procedure. Non-fasting spot urine samples were analyzed for 460 males and 541 females by inductively coupled plasma mass spectrometry (ICP-MS). Careful control was applied during collection, handling and analyses of the samples to avoid any contamination. RESULTS: Globally, the results indicate that the exposure levels of the Belgian population to these TEs are low and grossly similar to those recently published by other national surveys. CONCLUSIONS: These new reference values and upper reference limits will be useful for future occupational and/or environmental surveys.