CXCR4 PET/MRI for follow-up of gastric mucosa-associated lymphoid tissue lymphoma after first-line Helicobacter pylori eradication.

Posttreatment evaluation of gastric mucosa-associated lymphoid tissue (MALT) lymphoma currently relies on esophagogastroduodenoscopy with histological assessment of biopsies. Overexpression of the G protein-coupled C-X-C chemokine receptor type 4 (CXCR4) has been previously observed in MALT lymphoma. The aim of this prospective study was to evaluate positron emission tomography (PET) with the novel CXCR4 tracer [68Ga]Pentixafor as a potential alternative to follow up biopsies for assessment of residual disease (noncomplete remission [CR]) after first-line Helicobacter pylori eradication. Forty-six post-H pylori eradication [68Ga]Pentixafor-PET/magnetic resonance imaging (MRI) examinations of 26 gastric MALT lymphoma patients, and 20 [68Ga]Pentixafor-PET/MRI examinations of 20 control group patients without lymphoma, were analyzed. In the MALT lymphoma group, time-matched gastric biopsies were used as reference standard and showed CR in 6 cases. Pooled examination-based accuracy, sensitivity, specificity, and positive and negative predictive values of [68Ga]Pentixafor-PET for detection of residual gastric MALT lymphoma at follow-up were 97.0%, 95.0%, 100.0%, 100.0%, and 92.9%, respectively. Maximum and mean PET standardized uptake values showed moderate correlation with immunohistochemistry-based CXCR4+ cell counts, with correlation coefficients of r = 0.51 and r = 0.52 (P = .008 and P = .006). In summary, CXCR4 imaging with [68Ga]Pentixafor-PET may represent a promising test for assessment of residual gastric MALT lymphomas after H pylori eradication.

Phosphonate Chelators for Medicinal Metal Ions.

A family of phosphonate-bearing chelators was synthesized to study their potential in metal-based (radio)pharmaceuticals. Three ligands (H6phospa, H6dipedpa, H6eppy; structures illustrated in manuscript) were fully characterized, including X-ray crystallographic structures of H6phospa and H6dipedpa. NMR spectroscopy techniques were used to confirm the complexation of each ligand with selected trivalent metal ions. These methods were particularly useful in discerning structural information for Sc3+ and La3+ complexes. Solution studies were conducted to evaluate the complex stability of 15 metal complexes. As a general trend, H6phospa was noted to form the most stable complexes, and H6eppy associated with the least stable complexes. Moreover, In3+ complexes were determined to be the most stable, and complexes with La3+ were the least stable, across all metals. Density functional theory (DFT) was employed to calculate structures of H6phospa and H6dipedpa complexes with La3+ and Sc3+. A comparison of experimental 1H NMR spectra with calculated 1H NMR spectra using DFT-optimized structures was used as a method of structure validation. It was noted that theoretical NMR spectra were very sensitive to a number of variables, such as ligand configuration, protonation state, and the number/orientation of explicit water molecules. In general, the inclusion of an explicit second shell of water molecules qualitatively improved the agreement between theoretical and experimental NMR spectra versus a polarizable continuum solvent model alone. Formation constants were also calculated from DFT results using potential-energy optimized structures. Strong dependence of molecular free energies on explicit water molecule number, water molecule configuration, and protonation state was observed, highlighting the need for dynamic data in accurate first-principles calculations of metal-ligand stability constants.

Reversible Chemosensor for Bioimaging and Biosensing of Zn(II) and hpH in Cells, Larval Zebrafish, and Plants with Dual-Channel Fluorescence Signals.

Zinc/Zn(II) is an essential trace element for humans and acts as an important substance that maintains the normal growth, development, and metabolism of the body. Excess or deficient Zn(II) can cause abnormal metabolism in the human body, leading to a series of diseases. Moreover, biosystems have complex homeostasis systems, especially harsh pH (OH-) environments. Thus, investigating the variation in the levels of Zn(II) and OH- is extremely important in clinical, medical, and environmental testing. Nevertheless, the lack of practical and convenient fluorescence imaging tools limits the tracing of Zn(II) and OH- in biosystems. In this work, a well-designed dual-channel fluorescent signal response chemosensor (DACH-fhba) was assembled for selective sensing of Zn(II) and OH- in the biosystem using a fluorescence turn-on strategy. On encountering Zn(II), the chemosensor emitted a blue fluorescence signal (455 nm). Meanwhile, the bright green fluorescence signal (530 nm) increased with OH- addition simultaneously. With the blue/green dual fluorescence response of DACH-fhba, the sensor exhibited high stability and reversibility. Notably, the bioimaging revealed that DACH-fhba successfully tracked Zn(II) and OH- in live cells, larval zebrafish, and plants. Further results implied that DACH-fhba can be used to achieve visual detection of Zn(II) and OH- in organisms. Altogether, this work is conducive to the monitoring of Zn(II) and OH- in organisms and promotes the understanding of the function of Zn(II) and OH- in biosystems.

Direct distinction of ibuprofen and flurbiprofen enantiomers by ion mobility mass spectrometry of their ternary complexes with metal cations and cyclodextrins in the gas phase.

Enantiomeric drugs are widely used and play important roles in pharmaceuticals. Ion mobility spectrometry coupled with mass spectrometry technology provides a unique method for distinguishing the enantiomeric drugs, enantiomeric identification, and quantitation in the gas phase. In this study, enantiomeric molecules of ibuprofen and flurbiprofen were clearly recognized by forming host-guest complex ions using trapped ion mobility time-of-flight mass spectrometry. Ternary complex ions can be produced easily by electrospray ionization of the mixed solutions of ibuprofen, cyclodextrins, and CaCl2 , LiCl, or NaCl, as well as flurbiprofen, cyclodextrins, and CaCl2 . The relative contents of different chiral ibuprofens in a mixed solution were also quantitatively measured. This new method is a simple, effective, and a convenient enantioselective analysis method.

Targeted Luminescent Europium Peptide Conjugates: Comparative Analysis Using Maleimide and para-Nitropyridyl Linkages for Organelle Staining.

The syntheses and photophysical behavior of nine strongly luminescent nonadentate Eu(III) complexes are reported. Each complex is based on N-functionalized 1,4,7-triazacyclononane, and linkage to other groups or targeting vectors can occur either via amide bond formation to a coordinated pyridine p-aminopropyl group or via a nucleophilic substitution reaction involving thiol attack on a metal coordinated p-nitropyridyl moiety. Evidence is presented in favor of the latter conjugation strategy, as parallel work with maleimide conjugates was complicated or compromised by the propensity to undergo post-conjugation thiol exchange or succinimide ring hydrolysis reactions. Confocal microscopy and spectral imaging studies revealed that the peptide conjugate of AcCFFKDEL was found to localize selectively in the endoplasmic reticulum of mouse fibroblast cells, whereas the related maleimide conjugate was only observed in cellular lysosomes.

Metal-Ligand Coordination Nanomaterials for Biomedical Imaging.

Over the past two decades, amorphous nanoscale coordination polymers (NCPs) and crystalline nanoscale metal-organic frameworks (NMOFs) have emerged as attractive nanomaterials in biomedical applications, especially in drug delivery, biomedical imaging, and biosensing. The biodegradability, tunable composition, and feasible functionality of NCPs/NMOFs make them excellent contrast agents or nanocarriers for biomedical imaging, including magnetic resonance (MR) imaging, positron emission tomography (PET), computed tomography (CT), optical imaging, and photoacoustic (PA) imaging. In this Topical Review, we will summarize the recent advances of NCPs/NMOFs in biomedical imaging with emphasis on research over the past three years. A variety of imaging technologies based on NCPs/NMOFs will be discussed, followed by the introduction of the application of NCPs/NMOFs in multimodal imaging where optical/MR imaging is highlighted. In the final part, we will make concluding remarks and point out the challenges and prospects for the further development in this area of research.

Iridium(III)-based chemosensors for the detection of metal ions.

In recent years, transition metal complexes with their prominent photophysical properties have emerged as versatile chemosensors to probe different target analytes, including metal ions. By incorporating specific metal ion receptors, various iridium(III) complex-based cation sensors have been developed using different mechanisms. In this review, we survey examples of iridium(III) complex-based metal ion chemosensors that have been reported in the literature. Their design, mechanism and outlook will also be discussed.

Fulvic acids from Amazonian anthropogenic soils: Insight into the molecular composition and copper binding properties using fluorescence techniques.

Fulvic acids (FA) are one of the components of humic substances and play an important role in the interaction with metallic species and, consequently, the bioavailability, distribution and toxicity of metals. However, only a few studies have investigated these FA properties in specific environment, such as anthropogenic soils. Therefore, knowledge about FA molecular composition as well as the FA-metal interaction is essential to predict their behavior in the soil. For this reason, the aim of this study was to investigate the molecular composition of FA extracted from two sites in an anthropogenic soil (Terra Mulata), from the Amazon region, as well as their interactions with Cu(II) ions as a model. Results from 13C NMR, infrared and elemental analysis showed that these FA are composed mostly by alkyl structures and oxygen-functional groups, e.g., hydroxyl, carbonyl and carboxyl. The interaction with Cu(II) ions was evaluated by fluorescence quenching, in which the FA showed both high quantity of complexing sites per gram of carbon and good affinity to interact with the metal when compared with other soil FA. The results showed that the complexation capacity was highly correlated by the content of functional groups, while the binding affinity was largely influenced by structural factors. In addition, through the lifetime decay given by time-resolved fluorescence, it was concluded that static quenching took place in FA and Cu(II) interaction with the formation of a non-fluorescent ground-state complex. Therefore, this fraction of soil organic matter will fully participate in complexation reactions, thereby influencing the mobility and bioavailability of metal in soils. Hence, the importance of the study, and the role of FA in the environment, can be seen especially in the Amazon, which is one of the most important biomes in the world.

Intramolecular and Metal-to-Molecule Charge Transfer Electronic Resonances in the Surface-Enhanced Raman Scattering of 1,4-Bis((E)-2-(pyridin-4-yl)vinyl)naphthalene.

Electrochemical surface-enhanced Raman scattering (SERS) of the cruciform system 1,4-bis((E)-2-(pyridin-4-yl)vinyl)naphthalene (bpyvn) was recorded on nanostructured silver surfaces at different electrode potentials by using excitation laser lines of 785 and 514.5 nm. SERS relative intensities were analyzed on the basis of the resonance Raman vibronic theory with the help of DFT calculations. The comparison between the experimental and the computed resonance Raman spectra calculated for the first five electronic states of the Ag2-bpyvn surface complex model points out that the selective enhancement of the SERS band recorded at about 1600 cm-1, under 785 nm excitation, is due to a resonant Raman process involving a photoexcited metal-to-molecule charge transfer state of the complex, while the enhancement of the 1570 cm-1 band using 514.5 nm excitation is due to an intramolecular π→π* electronic transition localized in the naphthalenyl framework, resulting in a case of surface-enhanced resonance Raman spectrum (SERRS). Thus, the enhancement of the SERS bands of bpyvn is controlled by a general chemical enhancement mechanism in which different resonance processes of the overall electronic structure of the metal-molecule system are involved.

Analysis of ruthenium anticancer agents by MEEKC-UV and MEEKC-ICP-MS: Impact of structural motifs on lipophilicity and biological activity.

We present here the first comprehensive study on the lipophilicity of ruthenium anticancer agents encompassing compounds with broad structural diversity, ranging from octahedral RuIII (azole) through to RuII (arene) complexes. MEEKC was used to determine the capacity factors of the Ru complexes, and after a complex peak was unambiguously assigned using MEEKC-ICP-MS, the results were validated through comparison with the log P determined by octanol/water partitioning experiments. Correlation of the two data sets demonstrated a close relationship despite the limited structural overlap of the compounds studied. The capacity factors found by MEEKC allowed for the clustering of complexes based on their structure and this could be used to rationalize the observed cytotoxicity in the human colon carcinoma HCT116 cell line. It was demonstrated that rather than modification of the mono- or bidentate coordinated ligands much tighter control over a complexes lipophilic properties could be achieved through modification of the Ru(arene) ligand, with minimal detriment to cytotoxicity. This demonstrates the flexibility and potential of the Ru piano-stool scaffold. MEEKC proved to be a highly efficient means of screening the anticancer potential of preclinical ruthenium complex candidates for their lipophilic properties and correlate them with their biological activity and structural properties.

Preparation of iron-based MIL-101 functionalized polydopamine@Fe3 O4 magnetic composites for extracting sulfonylurea herbicides from environmental water and vegetable samples.

Here, we describe a simple one-pot solvothermal method for synthesizing MIL-101(Fe)@polydopamine@Fe3 O4 composites from polydopamine-modified Fe3 O4 particles. The composite was used as a magnetic adsorbent to rapidly extract sulfonylurea herbicides. The herbicides were then analyzed by high-performance liquid chromatography. The best possible extraction efficiencies were achieved by optimizing the most important extraction parameters, including desorption conditions, extraction time, adsorbent dose, salt concentration, and the pH of the solution. Good linearity was found (correlation coefficients >0.9991) over the herbicide concentration range 1-150 µg/L using the optimal conditions. The limits of detection (the concentrations giving signal/noise ratios of 3) were low, at 0.12-0.34 µg/L, and repeatability was good (the relative standard deviations were <4.8%, n = 6). The method was used successfully to determine four sulfonylurea herbicides in environmental water and vegetable samples, giving satisfactory recoveries of 87.1-108.9%. The extraction efficiency achieved using MIL-101(Fe)@polydopamine@Fe3 O4 was compared with the extraction efficiencies achieved using other magnetic composites (polydopamine@Fe3 O4 , Hong Kong University of Science and Technology (HKUST)-1@polydopamine@Fe3 O4 , and MIL-100(Fe)@polydopamine@Fe3 O4 ). The results showed that the magnetic MIL-101(Fe)@polydopamine@Fe3 O4 composites have great potential for the extraction of trace sulfonylurea herbicides from various sample types.

The complexation of rhizosphere and nonrhizosphere soil organic matter with chromium: Using elemental analysis combined with FTIR spectroscopy.

Complexation is a main mechanism controlling the reactions between soil organic matter (SOM) and heavy metals, which still have not been fully understood up to date. The objective of this study was to compare the SOM composition of nonrhizosphere and rhizosphere in low Cr treatment with that in high Cr treatment and to find out how metal concentrations affect the complexation with SOM. The results revealed that both the hydroxyl and the carboxyl were significantly different under different Cr treatment groups. For nonrhizosphere samples, the high Cr treatment tended to have less hydroxyl contents and more structural changes on hydroxyl (3389-3381 cm-1) than the low Cr treatment (3389-3388 cm-1), while in the rhizosphere samples the reverse happened. The gap of the different Cr treated band area in the rhizosphere samples (44 a.u of the gap) was greatly smaller than that in the nonrhizosphere samples (576 a.u of the gap). In both the rhizosphere and nonrhizosphere samples, the high Cr treatment showed greater structural changes on carboxylic acids (11, 12 a.u changes based on the control) than the low Cr treatment (4, 6 a.u). The unsaturated carboxylic acids could account for downward frequency shift and the contents in the nonrhizosphere samples were slightly greater than that in the rhizosphere samples. This study used elemental analysis combined with FTIR spectroscopy to explore the effects of metal concentrations on the complexation of Cr with SOM and the composition of SOM. These findings give a way to understanding part of the complexation mechanisms between the metal and SOM.

Nature differences of humic acids fractions induced by extracted sequence as explanatory factors for binding characteristics of heavy metals.

The composition and structure of Humic acid (HA) is so heterogeneous that it brings significant barriers to investigate the interaction between HA and heavy metal ions. The isolation of HA with relatively homogeneity is a key to reveal the binding mechanisms between HA and heavy metals. In this work, ten HA fractions (HAs) were obtained by sequential alkali extraction procedure and nature differences of the extracted HAs were considered as explanatory factors for binding characteristics of Cu2+, Pb2+ and Cd2+. The results indicate that more large molecular weight (MW) HA subunits, less carboxyl and phenolic group contents, weaker aromaticity and polarity were measured with increasing extractions, inducing weaker binding capacity of HAs. Ligand binding and bi-Langmuir models indicated that the sorption capacity and binding affinity of earlier extracted HAs were higher than the latter ones. The peak area changes at 3427, 1599, and 619 cm-1 pre- and post-adsorption in FTIR spectra suggested carboxyl, phenolic and nitrogen-containing groups were involved in the adsorption process. At the same time, the peak area difference between HAs and HAs-metal (ΔS) of phenolic groups were 8.22-20.50, 6.81-21.11 and 10.66-19.80% for Cu2+, Pb2+ and Cd2+, respectively, ΔS of carboxyl groups 6.64-17.03, 8.96-16.82 and 9.45-17.85% for Cu2+, Pb2+ and Cd2+, respectively, ΔS of nitrogen-containing groups 0.33-0.48, 0.20-1.38 and 0.31-0.59% for Cu2+, Pb2+ and Cd2+, respectively. ΔS of phenolic and carboxyl groups were larger than those of nitrogen-containing groups, implying that these two groups were the predominant binding sites suppliers for metal ions, which were also supported by the results of correlation analysis. This work is helpful to insight the environmental impacts of natural organic matter and the fate of heavy metals in natural environment.

Aquatic Humic Substances: Relationship Between Origin and Complexing Capacity.

Aiming to determine the relationship between source and complexing capacity, humic substances obtained from three sites (Sorocaba and Itapanhau Brasilian rivers, and Xochimilco Lake in Mexico) were studied. Copper, manganese, zinc and arsenic complexing capacity were determined for the three substances under various pH conditions. Results showed similar complexing capacity for the three elements depending on the chemistry of each one and on the physico-chemical conditions. Speciation diagrams showed that these conditions affect both, the humic substances, and the transition metals and arsenic.

Spectroscopic and cytotoxic studies of losartan complexes.

Use of drug-metal complexes for the treatment of several human diseases has resulted in significant progress in the field of medicinal inorganic chemistry. The current study describes the synthesis and characterization of Cu (II) and Ni (II) complexes of Losartan, an antihypertensive drug. These complexes were evaluated for their cytotoxic activity against four human cancer cell lines; SNB-19, HCT-15, COLO-205 and KB-3-1. Spectroscopic characterization revealed that during complex formation, the metal was bound through the nitrogen atoms of the tetrazole moiety of the losartan molecule. The molecular formulas of copper ([Cu (LS) 2 Cl2].6H2O) and nickel ([Ni (LS) 2Cl2]. H2O) complexes were found to be in agreement with the analytical data obtained through elemental analysis. For both the complexes, metal to ligand ratios of 1:2 were calculated. As revealed by FTIR, UV-Visible, and 1H-NMR studies, both the complexes displayed octahedral geometries. Scanning electron microscopy (SEM) revealed marked changes in the morphology of the complexes, compared to the pure drug. From XRD studies, characteristic crystalline peaks of pure losartan were observed whereas no prominent peaks were observed for its complexes. Complexes were found to be inactive in the cytotoxic activity test performed using SNB-19, HCT-15, COLO-205 and KB-3-1 cell lines.

Europium (III) and Uranium (VI) complexation by natural organic matter (NOM): Effect of source.

For the safe long-term storage of high-level radioactive waste (HLW), detailed information about geo-chemical behavior of radioactive and toxic metal ions under environmental conditions is important. Natural organic matter (NOM) can play a crucial role in the immobilization or mobilization of these metal ions due to its complexation and colloid formation tendency. In this study, the complexation of europium (as chemical homologue of trivalent actinides such as americium) and uranium (as main component of HLW) by ten humic acids (HA) from different sources and Suwannee NOM river extract has been analyzed. Capillary electrophoresis in combination with inductively coupled plasma mass spectrometry has been used for the evaluation of complex stability constants log ß. In order to determine the complex stability constants a conservative single site model was used in this study. In dependence of their source and thus of NOM structure the log ß values for the analyzed humic acids are in the range of 6.1-7.0 for Eu(III) and 5.2-6.4 for U(VI) (UO22+ ), respectively. In contrast to the results for HA the used Suwannee river NOM reveals log ß values in the range of nearly two orders of magnitude lower (4.6 for Eu3+ and 4.5 for UO22+ ) under the geochemical conditions applied in this study.

HPTLC and magnetochromatography of new complexes of carboxylates with transition metals or rare earth elements and their ligands - study of lipophilicity.

Nineteen new complexes of carboxylates with transition and rare elements as central ions and their ligands were characterized by chromatographic analyses. The parameter of relative lipophilicity (RM0 ) of the tested compounds was determined experimentally by the reversed-phase high-performance thin layer chromatography method with mixtures of various organic modifiers (acetonitrile, acetone, dioxane) and water as a mobile phase. The extrapolated RM0 values were compared with the logP values calculated from the molecular structures of tested solutes. Similarities between the lipophilicity indices were analysed by principal component analysis and linear regression. Thin-layer chromatography combined with a magnetic field has been proposed as a complementary method for determination of lipophilicity of the investigated compounds. The chromatograms in the field and outside it were developed simultaneously in two identical chromatographic chambers. One of them was placed in the external magnetic field of 0.4 T inductivity. We proved that chelation causes a drastic change in compound lipophilicity, but all complexes did not exhibit enhanced activity as compared with the parent ligand. Also in the magnetic field the retention of some complexes changed, which means that the presence of the field influences the physicochemical properties of the compounds and their interactions with the stationary phase.

Decolorization of acid, disperse and reactive dyes by Trametes versicolor CBR43.

The mycoremediation has been considered as a promising method for decolorizing dye wastewater. To explore new bioresource for mycoremediation, a new white-rot fungus that could decolorize various dyes commonly used in textile industries was isolated, and its ligninolytic enzyme activity and decolorization capacity were characterized. The isolated CBR43 was identified as Trametes versicolor based on the morphological properties of its fruit body and spores, as well as through partial 18S rDNA gene sequences. Isolated CBR43 displayed high activities of laccase and Mn-dependent peroxidase, whereas its lignin peroxidase activity was relatively low. These ligninolytic enzyme activities in potato dextrose broth (PDB) medium were enhanced by the addition of yeast extract (1-10 g L-1). In particular, lignin peroxidase activity was increased more than 5 times in the PDB medium amended with 10 g L-1 of yeast extract. The CBR43 decolorized more than 90% of 200 mg L-1 acid dyes (red 114, blue 62 and black 172) and reactive dyes (red 120, blue 4, orange 16 and black 5) within 6 days in the PDB medium. CBR43 decolorized 67% of 200 mg L-1 acid orange 7 within 9 days. The decolorization efficiencies for disperse dyes (red 1, orange 3 and black 1) were 51-80% within 9 days. The CBR43 could effectively decolorize high concentrations of acid blue 62 and acid black 172 (500-700 mg L-1). The maximum dye decolorization rate was obtained at 28°C, pH 5, and 150 rpm in the PDB medium. T. versicolor CBR43 had high laccase and Mn-dependent peroxidase activities, and could decolorize a wide variety of dyes such as acid, disperse and reactive textile dyes. This fungus had decolorizing activities of azo-type dyes as well as anthraquinone-type dyes. T. versicolor CBR43 is one of promising bioresources for the decolorization of textile wastewater including various dyes.

An assessment of metal-humus complexes in river waters of the Upper Amur basin, Russia.

The dissolved metal concentrations have been assessed for Co, Cr, Cu, Fe, Mn, Ni, V, Zn, Ca, Mg, and Cd, and their complex compounds with humic substances (Me-HS complexes) in river waters of the Upper Amur basin using the inductively coupled plasma-mass spectrometry technique. The study shows an increase in the amount of Me-HS complexes from the southwestern steppe and forest-steppe to the northeastern mountainous taiga areas. In alkali waters of the steppe and forest-steppe areas with low concentrations of HS, the amount of Zn-HS complexes increases considerably. The observed general regularity in the distribution of metals is as follows: Fe > Cu ≥ Zn > Cr > V > Ni > Ð¡o ≥ Mn > Ca > Mg > Cd. In acidic and neutral waters of the taiga rivers containing high concentrations of HS, 50% of metals are complexed with HS. Metals are arranged in the following order: Fe > Cu > Ni > Cr > V > Zn > Ð¡o > Mn > Ca > Mg > Cd. Quantitative characteristics and a correlation matrix show that Me-HS complexes are dominant among toxic metals (Ni, Cu, Zn, Cr, Fe, and V) and account for 40-55% of total dissolved forms. This allows us to evaluate the important role of Me-HS complexes in satisfactory ecological situation in rivers of the Upper Amur basin. However, toxicity may increase in separate watercourses (Chita and Argun rivers) due to high concentrations of dissolved Zn, Cu, and Cr, which indicate local and transboundary sources of pollution.

[Metals and their compounds as contaminants in food : Arsenic, cadmium, lead and aluminum]. / Metalle und ihre Verbindungen als Kontaminanten in Lebensmitteln : Arsen, Cadmium, Blei und Aluminium.

Metals and their compounds are ubiquitously distributed in the environment, thus reaching plant and animal derived food. While actual exposure levels in Europe do not give rise to concern for acute toxicity, chronic toxicity of some metals and metalloids cannot be completely ruled out. Thus, in the case of inorganic arsenic, an elevated risk of carcinogenicity in different organs cannot be excluded even under actual dietary exposure conditions. In the case of cadmium, nephrotoxicity may be a particular problem for certain subgroups, such as children. Regarding lead, exposure levels have dropped considerably during the last two decades; nevertheless, developmental neurotoxicity may still be a problem during prenatal development and early childhood. Also in the case of aluminum current dietary exposure levels are close to the tolerable weekly intake (TWI) value derived by the European Food Safety Authority (EFSA). Taken together, for all four examples, further reductions in exposure levels are required.