Volume 82, Issue 2

Diet is the main source of trace elements, and exposure to dietary trace elements has a direct impact on the health of hundreds of millions worldwide. Insufficient intake of essential trace elements is a global issue. Deficiencies of iron, zinc, iodine, and selenium result in millions of people being affected by various diseases, with very serious consequences in those countries where malnutrition is widespread. On the other hand, the impact of toxic element species such as inorganic arsenic and methylmercury on entire populations has come to the fore again as a priority for both the scientific community and health authorities. The presence of trace elements in feeds, either as contaminants or as nutritional or zootechnical additives, and their transfer across the food chain to humans also raises questions within the scientific community and regulators. Different facets of trace elements, from essentiality to toxicity, were addressed throughout the 3rd International IUPAC Symposium on Trace Elements in Food (TEF-3). The meeting was organized by the Istituto Superiore di Sanità and held on 1-3 April 2009 in Rome, Italy. The objective was to gather experts with different backgrounds to discuss all aspects of trace elements in food in relation to human health, with special emphasis on biological effects of elements. The main topics included essentiality, toxicity, bioaccessibility, bioavailability, speciation, sources and transfer in the food chain, effects of processing, food and feed fortification, supplementation, international legislation and standards, analytical developments, analytical quality assurance and reference materials. In accordance with practice in previous events of this series (Warsaw, 2000, and Brussels, 2004), TEF-3 provided a forum for the exchange of new ideas and experiences in trace element research, and a basis for influencing policy, advisory practice, and risk-management tools to protect public health. Over 200 participants, representing some 40 countries, joined the event. In addition to the 15 invited lectures, delegates from Europe, Asia, Africa, North and South America enriched this edition with 20 oral and about 130 poster contributions. TEF-3 actually resulted in a lively interdisciplinary symposium on current and emerging research and development efforts. Special emphasis was placed on the following topics: - analytical techniques for element speciation studies in food and food supplements - reliability and quality control of analytical data on trace elements in foodstuffs - detection, characterization, and potential health risks of inorganic nanoparticles - arsenic speciation and toxicology - gender differences in susceptibility to toxic trace elements in food - exposure assessment of toxic element species - assessment of risks and benefits of the organic forms of trace elements as feed additives - metabolism of metal(loid)s by intestinal microorganisms - absorption and metabolism of iron, zinc, and other essential elements - use of stable isotopes to study trace mineral metabolism - selenium and iodine speciation and biological effects Advancements in the above-mentioned areas were discussed, and special attention was paid to the means in order to prevent adverse health effects on those individuals and populations most vulnerable to trace-element inadequacies, excesses, or imbalances. The following collection of papers based upon authoritative lectures presented at TEF-3 addresses many of the topics discussed during the symposium. Overall, it provides an excellent overview of the state of the art in the area of trace elements in food and sheds light on future challenges and subjects of research. Francesco Cubadda Conference Chair

With the rapid development of nanotechnology, the presence of nanoparticles (NPs) in commercially available products is becoming more and more common. The field of food nanotechnology has experienced significant growth over the last five years. Agricultural cultivation, food processing, food packaging, food security, and water purification are examples of the important sectors linked with nanotechnology in the food production chain. However, safety concerns about such nanotechnology and the use of nanomaterials are increasing. Many determinants for the unusual activities and toxicities of the nanomaterials involving particle size, chemical composition, surface structure, and dosage are considered as well as three main exposure routes, including inhalation, ingestion, and dermal exposure. In addition, the trends and progress for toxicity and risk evaluation of the nanomaterials used in the food industry are also reviewed, which are helpful to understand and establish a regulatory system for the further development and use of NPs in the food industry.

The presence of arsenic in marine samples was first reported over 100 years ago, and shortly thereafter it was shown that common seafood such as fish, crustaceans, and molluscs contained arsenic at exceedingly high concentrations. It was noted at the time that this seafood arsenic was probably present as an organically bound species because the concentrations were so high that if the arsenic had been present as an inorganic species it would certainly have been toxic to the humans consuming seafood. Investigations in the late 1970s identified the major form of seafood arsenic as arsenobetaine [(CH 3 ) 3 As + CH 2 COO – ], a harmless organoarsenic compound which, following ingestion by humans, is rapidly excreted in the urine. Since that work, however, over 50 additional arsenic species have been identified in marine organisms, including many important food products. For most of these arsenic compounds, the human toxicology remains unknown. The current status of arsenic in seafood will be discussed in terms of the possible origin of these compounds and the implications of their presence in our foods.

Quality assurance of exposure biomarkers usually focuses on laboratory performance only. Using data from a prospective birth cohort study in the Faroe Islands, we have assessed the total imprecision of exposure biomarkers. As biomarkers of prenatal methylmercury exposure, mercury concentrations were determined in cord blood, cord tissue, and maternal hair. We determined their mutual correlations and their associations with the child’s neurobehavioral effect variables at age 7 years. The exposure biomarkers correlated well with one another, but the cord-blood mercury concentration showed the best associations with neurobehavioral deficits. Because at least three exposure parameters were available, factor analysis and structural equation modeling could be applied to determine the total imprecision of each biomarker. For the cord-blood parameter, the total imprecision was 25–30 %, and almost twice as much for maternal hair. The total imprecision of these biomarkers much exceeded the normal laboratory variability of less than 5 %. Such imprecision can cause underestimation of dose-related toxicity, and data analysis should therefore include sensitivity analyses that take this factor into account. Ignoring preanalytical imprecision may cause serious bias.

Essential trace elements (TEs) are major nutritional feed additives, required for the health and welfare of farm animals, especially under intensive husbandry conditions. Within the European Food Safety Authority (EFSA), risk assessment of feed additives is carried out by the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP), which is increasingly confronted with additives based on organic forms of TEs. Organic forms are expected to have higher bioavailability, hence, lower levels in feeds may be needed to meet farm animal requirements. On the other hand, higher bioavailability might also lead to enhanced deposition in edible tissues, hence, increased consumer exposure; specific organic forms might also have a different distribution in edible tissues or products. Higher consumer exposure is especially relevant to TEs with recognized health risks at excess levels (e.g., Se); exposure scenarios should take into account background dietary levels and other intake sources (e.g., supplements). Tolerable upper intake levels (ULs) for adults and children are the basis for risk assessment; when no UL is defined (e.g., for Mn), a conservative estimate should assess whether the organic form in feeds might significantly increase the consumer’s intake above the dietary background. In perspective, specific maximum allowable contents might be considered for organic forms of TEs in feeds, when supported by a robust database as well as by targeted analytical methods.

Many metals and metalloids undergo complex biotransformation processes by micro-organisms in the environment, namely, Ge, As, Se, Cd, In, Sn, Sb, Te, Hg, Tl, Pb, Bi, and Po. Though the human intestine harbors a highly diverse and metabolically active micro-bial community, the knowledge on metal(loid) biotransformation by gut microbiota is limited. Microbial metal(loid) metabolism in the gut is highly relevant when assessing health risks from oral exposure, as both the bioavailability and the toxicity of the ingested compound can be modulated. This review gathers and compares a broad selection of scientific studies on the intestinal biotransformation of metal(loid)s. It can be inferred that metal(loid) biotransformation by intestinal microbiota is a common process, resulting in both beneficial and adverse toxicological effects. Whereas for Hg the intestinal demethylation of methylmercury results in enhanced elimination, highly bioavailable and toxic arsenic and Bi species are formed by intestinal microorganisms. In either case, we conclude that the gut microbial potency should be considered to be taken up in toxicokinetic studies and models for assessing the health risks of oral metal(loid) exposure. This will allow the relevance of intestinal metal(loid) biotransformation to be assessed for human health risks. Keywords : colon microflora; biomethylation; metals; metalloids; risk assessment; speciation; thiolation; volatilization.

Iron is known to be absorbed from foods in two major forms, heme iron and non-heme iron. Iron status as well as dietary factors known to affect iron absorption has limited effect on heme iron absorption, whereas inhibitors and enhancers of iron absorption have pronounced effects on non-heme iron absorption. The enterocyte transporter for non-heme iron, DMT1, is strongly up-regulated during iron deficiency and down-regulated during iron overload. A transporter for heme iron, HCP1, was recently characterized and is present on the apical membrane of enterocytes. Two other pathways for iron absorption have been discovered and may serve to facilitate uptake of iron from two unique iron-binding proteins, lactoferrin and ferritin. Lactoferrin is an iron-binding protein in human milk and known to survive proteolytic digestion. It mediates iron uptake in breast-fed infants through endocytosis via a specific lactoferrin receptor (LfR). Recently, lactoferrin has become popular as a food additive and may enhance iron status in several age groups. Ferritin is present in meat, but also in plants. The ferritin content of plants can be enhanced by conventional breeding or genetic engineering, and thereby increase iron intake of populations consuming plant-based diets. Ferritin is a bioavailable source of iron, as shown in recent human studies. Ferritin can be taken up by intestinal cells via endocytosis, suggesting a receptor-mediated mechanism.

Mineral requirements in young children are poorly understood, and current recommendations rely heavily on data collected in older children or adults. Our objectives were to assess the relationship between mineral (Ca, Mg, Fe, Zn, and Cu) intake in young U.S. children, and mineral absorption, excretion, and retention; and to use these data to re-examine the most recent recommended intakes. Thirty children, 1–4 y old, were studied on their usual diet. After 7 d of home adaptation they were admitted for either a 2-d or 5-d metabolic study where multiple stable isotope or Ca, Mg, Fe, Zn, and Cu were administered and mineral absorption (2-d study), or absorption and excretion (5-d study) were assessed. Fractional (%) absorption of some (Ca, Mg) but not all (Fe, Zn) minerals decreased as intake increased. Absolute (total) absorption and net retention of all the minerals increased as their intake increased. Mineral homeostasis was related to changes in fractional absorption (Ca and Mg), fecal excretion (Zn), or whole body mineral status (Fe). Our results support the current U.S. recommended intakes for 1–4-y-old children for Mg and Fe, but suggest that those for Ca and Zn are too low.

Human breast milk can be considered as “ideal” food for the correct development of newborn babies and, for those that are not breast-fed, formula milk has to be used instead. Ideally, the composition of such formula milk preparations should closely resemble that of maternal human milk. Considerable differences between both in the total content of trace elements such as Fe, Cu, Se, Zn, and I and in their chemical form in both milk types have been demonstrated. Speciation analysis in milk whey was carried out first by high-performance liquid chromatography (HPLC) with inductively coupled plasma-mass spectrometry (ICP-MS) elemental detection and showed that the observed element distribution patterns were very different in the investigated human and formula milks. Using complementary molecular mass techniques (i.e., MALDI-TOF), the identity and chemical characterization of some biomolecules (e.g., protein) with which metals are associated in each fraction was also established (by a typical heteroatom-tagged proteomics protocol). Attempts to assess the nutritional value of elemental supplements in formula milk with the aid of quantitative chemical speciation, using stable isotopes in combination with ICP-MS and isotope pattern deconvolution (IPD), proved to be successful to differentiate and quantify endogenous (natural) and exogenous (supplemented) Se or Fe trace levels. In particular, the application of such ICP-MS based techniques to study Se bioavailability from formula milk and metabolism in Se-supplemented lactating rats is discussed in detail. Quantification of selenospecies of endogenous (natural) and exogenous (supplement) Se in rat’s urine is demonstrated and relevant information on possible Se biotransformations and its final catabolism from such results is discussed.

Selenium (Se) is an essential trace element to animals and humans as Se is incorporated in a series of organic molecules, such as 30 mammalian selenoproteins or seleno-enzymes, which are vital for the basic functions of life. To increase the Se intake in Se-deficient areas, food and feed can be enriched using Se fertilizers or supplements. The aim of this study is to investigate the distribution, speciation, bioaccessibility, and bioavailability of Se in Se-enriched wheat (SW) grain and in Se-enriched chicken meat products using commercial enzymes and human gastric juices (HGJs). Results from the present work show that Se in wheat is bioaccessible and bioavailable, and that SW flour or bran can serve as a valuable dietary source of Se to humans. However, the bioaccessibility studies using commercial enzymes and HGJs for wheat flour, bran, and chicken meat digestion suggests that the use of commercial enzymes overestimate Se bioavailability. Furthermore, the use of NaCl or Tris-HCl to extract Se proteins from enriched products was not suited for bioaccessibility studies. The SW flour or bran can, however, serve as a valuable dietary source of Se to humans.

The characterization of iodine species in the microalgae Chlorella vulgaris after cultivation with different potassium iodide concentrations was performed using the coupling of multidimensional chromatography (size exclusion chromatography, SEC, and anion exchange chromatography, AEC) with inductively coupled plasma-mass spectrometry (ICP-MS) detection. Two iodine fractions, water-soluble and macromolecular fractions, were obtained using a sequential extraction scheme based on chemical reagents. Most iodine species separated from the water-soluble fraction with SEC-ICP-MS (mass range from 0.5 to 100 kDa) are present in inorganic forms (peak III), although the other two peaks were detected (peaks I and II). The application of AEC to the isolated peak III fraction allows the characterization of IO 3 – (about 25 %) and I – (about 75 %). The application of SEC-ICP-MS (mass range from 10 to 1200 kDa) to the macromolecular fraction reveals the presence of four peaks from the void volume to about 67 kDa, a peak is located about 600 kDa. The mass balance of iodine in the different fractions obtained from the microalgae raw stuff shows that the water-soluble fraction represents 66.7 % of total iodine in microalgae, but the macromolecular fraction only contains 13.3 %, both summing up for 79.9 % of the total amount of iodine, which confirms the suitability of the separation scheme. Further studies have to be focused on the purification of the isolated fractions and their identification by tandem MS.

This document defines terms related to modern methods of radical polymerization, in which certain additives react reversibly with the radicals, thus enabling the reactions to take on much of the character of living polymerizations, even though some termination inevitably takes place. In recent technical literature, these reactions have often been loosely referred to as, inter alia, "controlled", "controlled/living", or "living" polymerizations. The use of these terms is discouraged. The use of "controlled" is permitted as long as the type of control is defined at its first occurrence, but the full name that is recommended for these polymerizations is "reversible-deactivation radical polymerization".

Definitions for the terms "metallome" and "metallomics" are proposed. The state of the art of analytical techniques and methods for systematic studies of metal content, speciation, localization, and use in biological systems is briefly summarized and critically evaluated.