Genotoxicity plays an important role in chemical safety assessment, as genetic alterations can lead to severe and irreversible health consequences. To date, the assessment of genotoxicity has mostly been limited to hazard identification, followed by rigorous risk mitigation measures if a substance is found to be mutagenic, regardless of potency, the underlying mechanism, and cellular biology. While this regulatory hazard-based approach is straightforward, it is unsatisfactory when exposure to genotoxic substances cannot be completely avoided and/or regulatory measures lead to misperceptions of risk and undesirable socioeconomic side effects. The latter becomes particularly obvious in light of natural genotoxicants, e.g. occurring in plant-based food, and for substances that are difficult to replace but come with a high socioeconomic value but little potency and exposure. Hence, there is an increasing demand for a paradigm shift towards a quantitative interpretation of genotoxicity data in regulatory risk assessment. However, moving away from the traditional hazard-based assessment and doing so safely requires a collective effort of all relevant stakeholders. To this end, the German Federal Institute for Risk Assessment (BfR) organised an international symposium, at which experts from regulatory authorities, academia and industry discussed the opportunities and challenges involved. Here, we present key issues to be considered for a successful implementation of quantitative approaches. In situations where exposure to genotoxic substances cannot be completely avoided, e.g. occurrence of contaminants, quantitative approaches offer the opportunity to better characterise the associated risks and thus enable risk managers to make more informed decisions.

Plant protection products (PPPs) contain active substances (AS) providing pesticidal activity and co-formulants supporting efficacy. AS undergo extensive safety assessment, including genotoxicity testing, while PPPs are assessed only for acute and local toxicity. Genotoxicity may contribute to long-term effects like carcinogenesis, and as operators are exposed to concentrated PPPs and spray dilutions, co-formulant toxicity and interactions require attention. An in silico analysis was conducted to identify potentially genotoxic co-formulants and prioritise PPPs for in vitro testing. Four prioritised co-formulants exceeded 1 % concentration in eight PPPs, but existing data ruled out further investigation. AS with known in vitro genotoxic potential were assessed for toxicokinetic interaction with co-formulants. The genotoxic potential of PPPs containing metiram, a dithiocarbamate fungicide, and pendimethalin, a dinitroaniline herbicide, was assessed in V79 cells using in vitro micronucleus test. No difference was observed between metiram and its PPP, whereas a 2-fold increase in micronuclei formation occurred in formulated PPP compared to pendimethalin alone at highest tested concentration. These findings indicate that co-formulants, although unlikely to be genotoxic on their own, may influence the genotoxic potential of pendimethalin in the tested PPP. Therefore, AS showing genotoxic potential in vitro should be considered for testing in respective formulated PPPs.

Handgrip strength is an important marker of health status and is influenced by modifiable risk factors, including dietary intake. Trace elements (TE) copper, iron, iodine, manganese, selenium, and zinc are involved in physiological processes relevant to muscle function. However, the individual and interactive effects of these TE on handgrip strength have not been investigated in community-dwelling non-diabetic older adults. We performed a cross-sectional analysis within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort, comprising 1432 participants (median age 67 years, 59

Despite the widespread occurrence of arsenolipids in seafood, and studies with human cells demonstrating their cellular toxicity, the human health risks of ingesting these compounds are largely unknown. In this first experimental animal study we investigated the uptake, transformation and distribution of the arsenohydrocarbon 1-dimethylarsinoylpentadecane, one of the most abundant and cytotoxic arsenolipid present in seafood, in mice following oral exposure. The compound was extensively metabolized, mainly to dimethylarsinate, which was excreted predominantly in urine. Approximately 0.6% of the administered dose was retained in tissues, with the highest concentrations occurring in the brain, where arsenic was present as both the parent arsenohydrocarbon and its thio metabolite. These findings demonstrate that dietary arsenohydrocarbons can reach and persist in brain tissue, highlighting the need for comprehensive hazard assessment and human health risk evaluation of arsenolipids in seafood.

Older age combined with chronic disease increases the risk of malnutrition and frailty, impacting disease recovery and overall clinical outcomes. Serum concentrations of several trace elements and their respective biomarkers have not yet been investigated with regard to frailty in older adults with disease, although these patients most likely have an altered trace element profile owing to both inflammatory conditions and inadequate dietary intake. This cross-sectional study investigated trace element profiles in relation to age, disease, and frailty status in geriatric patients (n = 198) as well as in old (n = 80) and young (n = 60) healthy controls. Serum concentrations of iron, zinc, selenium, iodine, copper, and manganese were quantified via ICP-MS/MS, alongside inflammatory markers and functional biomarkers. Analysis revealed distinct trace element profiles in patients compared to healthy controls, with lower manganese, iron, zinc, and selenium, but higher copper and iodine (p ≤ 0.001). Trace element concentrations were similar in young and older healthy controls. Principal component (PC) analysis identified two profiles. PC1 was negatively associated with age, number of drugs, sex, and inflammation. Only PC2 was associated with anorexia (β = 0.053 ± 0.020; 95

BackgroundSerum trace elements, anthropometric data, and oxidative stress markers are often altered in patients diagnosed with Alzheimer's disease (AD) or other types of dementia (OTD). However, these parameters are rarely examined together before disease onset in a single study population.ObjectiveThis nested case-control study aims to investigate anthropometric data, serum trace elements, exchangeable copper (CuEXC), and oxidative stress markers to identify early associations with the risk of AD or OTD.MethodsFrom the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort (DRKS-ID: DRKS00020593), the High Fat Diet, Microbiota, and Neuroinflammation in the Progression of Alzheimer study was generated. One hundred twenty-eight individuals who developed AD or OTD were identified, approximately 15.7 years after baseline data collection, and matched for age, sex, fasting status, and season of blood sampling with 512 controls. Serum levels of manganese (Mn), iron (Fe), copper (Cu), zinc (Zn), selenium (Se), iodine (I), CuEXC, and plasma malondialdehyde (MDA) and 3-nitrotyrosine (3-NT) were analyzed.ResultsCases and non-cases did not differ in anthropometric data or oxidative stress markers. Female cases exhibited a trend of elevated serum Cu and CuEXC levels compared to female non-cases. A higher Se/Cu ratio suggested an inverse association (OR = 0.72, 95% CI: 0.56-0.92), while an increased Cu/Zn ratio was positively associated (OR = 2.1, 95% CI: 1.1-4.1) with AD or OTD incidence.ConclusionsRatios of serum trace elements, rather than individual levels, show early associations with the risk of AD or OTD while anthropometric and oxidative stress markers did not.

Copper (Cu) supplementation is essential in pig nutrition; however, its effects on performance, trace element accumulation in edible tissues, and environmental excretion require careful evaluation. In the present study a total of 24 male, castrated fattening pigs of two different hybrid mast lines (11 weeks of age) were divided according to their initial body weight (25.8 ± 3.5 kg) into four groups. Pigs were fed for 14 weeks a complete feed supplemented with Cu covering a range between the recommended Cu supplementation and the permissible European maximum level (i.e. 5, 15, and 25 mg/kg complete feed). Two different Cu sources were used: Cu sulphate (CuSO₄) and glycine-Cu chelate hydrate (Cu-Gly). The aim of the trial was studying the influence of the different Cu levels and sources on growth performance, Cu transfer to edible tissues (muscle, liver, kidney, blood) and faeces, as well as the concentration of other trace elements, including iron (Fe), zinc (Zn) and manganese (Mn) in tissues of fattening pigs. Performance parameters, including average daily gain (ADG) and feed conversion ratio (FCR), showed a dependency with respect to the pig breed, whereas Cu content and Cu sources showed no influence. Copper concentrations in the liver, kidney, muscle, and blood serum remained constant across groups. Faecal Cu excretion increased proportionally with dietary Cu levels, with higher excretion observed for the organic Cu source at 15 mg/kg as compared with inorganic source at similar level. The results show, that Cu levels up to the maximum level of 25 mg/kg complete feed are not necessary to achieve good growth performance in healthy fattening pigs. The unaffected Cu concentrations in liver, muscle, kidney, and blood, as well as increased faecal excretion with increasing Cu level in the feed, indicate an adequate supply and homoeostatic regulation of Cu. In addition, a reduced use of Cu in pig fattening will help to reduce Cu emission into the environment.

The widespread application of per- and polyfluoroalkyl substances (PFAS) resulted in ubiquitous environmental contamination. Understanding the PFAS tissue distribution in mammals and humans is crucial for the assessment of potential health risks. The levels of eleven PFAS were determined by UPLC-MS/MS in plasma and various tissues of wild boar (n = 82) hunted in Germany. The most prevalent PFAS (PFOA, PFNA, PFHxS and PFOS) were detected in all analyzed samples. The median level of the sum (Σ 4PFAS) was highest in liver (90.2 μg/kg), followed by kidney (9.45 μg/kg), plasma (7.63 μg/L), lung (6.84 μg/kg), heart muscle (2.60 μg/kg), spleen (2.46 μg/kg), and skeletal muscle (1.03 μg/kg). Consumption of a single portion (125 g) of liver containing the Σ 4PFAS median level would result in a 36.6-fold exceedance of the tolerable weekly intake (TWI) of EFSA in a 70 kg-person. The accumulation (calculated as tissue/plasma ratio) of perfluoroalkyl carboxylic acids with ηpfc = 8-13 in lung, spleen, muscle and heart tissues increased with molecule size, indicating passive mechanisms of distribution driven by hydrophobicity. In contrast, liver and kidney distribution coefficients scattered, indicating additional involvement of chain-length dependent active transport processes. The highest accumulation was observed for PFOS in the liver (median tissue/plasma ratio 18.0). The shortest PFAS included in the study (PFHxA, PFHpA, PFOA, PFBS and PFHxS) did not accumulate in any of the tissues, probably due to strong binding to blood proteins like serum albumin and their relative polarity impeding passive membrane diffusion.

The usage of cobalt (Co) and nickel (Ni) in numerous commercial, industrial, and military applications causes widespread exposure nowadays, and concerns are rising about adverse impacts on human health. Emphasis is on the respiratory system, with both metals classified as (possibly) carcinogenic upon inhalation by the International Agency for Research on Cancer (IARC), but limited data are available upon oral exposure. Therefore, this study aims to evaluate the in vitro genotoxicity of Co(II) and Ni(II) and their combination in HepG2 cells, since exposure of those environmental pollutants occurs realistically in concert. Here, Co(II) exposure led to the induction of single-strand breaks and oxidative DNA damage detected by the Comet assay as FPG-sensitive sites, while Ni(II) increased the abundance of γ-H2AX, an indicator for double-strand breaks. Notably, combined exposure to Co(II) and Ni(II) resulted in enhanced DNA damage, especially at the chromosomal level, with increased formation of micronuclei as well as polynucleated cells, indicating a stronger effect compared to single exposure. Furthermore, both metals induced the DNA damage response pathway PARylation. As this process involves the consumption of large amounts of cellular NAD+ after DNA damage, the energy state was assessed upon exposure with Co(II) and Ni(II). Current data indicate that especially Co(II) altered the cellular energy state. This study reveals distinct mechanisms of DNA damage exhibited by Co(II) and Ni(II), which were enhanced after a combined treatment. This highlights the need for further research to estimate the genotoxic potential of targeting cells upon oral intake with increasing environmental entry.

Trace elements such as copper, zinc, and selenium are essential micronutrients that play crucial roles in various physiological processes, mainly through their involvement in enzymes and regulatory proteins. A deficiency of any of these elements can impair physiological functions and lead to a range of symptoms. While copper deficiency is rare, e.g., vegans are particularly susceptible to inadequate intake of zinc and selenium. To investigate the effects of multiple simultaneous deficiencies, a feeding study was conducted in adult male and female C57BL/6Jrj mice receiving diets low in copper, zinc, and selenium. This approach enabled us to explore potential interactions between trace elements and to identify organ-specific effects based on their distribution profiles. We observed a substantial depletion of copper and selenium concentrations in the circulation and in almost all organs although to a varying extent. In contrast, zinc levels were well maintained and only declined in serum and bone. In line with the well-known antagonistic relationship between copper and zinc, our findings revealed that zinc deficiency mitigated symptoms of copper deficiency, which was most pronounced in female mice. Moreover, copper deficiency led to increased selenium concentrations in various organs, which, however, was not accompanied by generally higher selenoprotein expression. Therefore, it is essential to consider potential effects of single trace element deficiencies on other trace elements taking also combined effects into account.

AIMS:To examine whether zinc (Zn) and copper (Cu) status influence the association of estimated delta-5 desaturase (D5D), delta-6 desaturase (D6D), and stearoyl-CoA desaturase-1 (SCD1) activities with type 2 diabetes (T2D) risk. METHODS:We used a nested case-cohort design within the EPIC-Potsdam Study (n = 1979; 447 incident T2D cases). Desaturase activities were estimated using erythrocyte fatty acids (FA): D5D (20:4n-6/20:3n-6), D6D (18:3n-6/18:2n-6), and SCD1 (16:1/16:0 [SCD1-16], 18:1/18:0 [SCD1-18]). We evaluated associations between desaturases and serum Zn or Cu, assessed interactions between serum Zn or Cu and desaturase activities in Cox regression models for T2D risk, and examined modification by Zn transporter SLC30A8 genetic variant and metal-related polygenic risk scores. RESULTS:Higher serum Zn was significantly associated with lower SCD1-18 activity (β per 1 SD = -0.09). Zn status showed a non-linear modifying effect on the D5D-T2D relationship (p-interaction = 0.03), though an inverse D5D association was observable consistently across Zn levels. Serum Cu was positively associated with SCD1-16 (β = 0.13) and SCD1-18 (β = 0.08) and negatively associated with D5D activity (β = -0.13). Stronger inverse associations of higher D5D activity with T2D risk were observed at low Cu levels (HR 0.69, 95% CI 0.58-0.81) versus higher levels (HR 0.95, 95% CI 0.80-1.13) (p-interaction = 0.009). The SLC30A8 variant rs13266634 significantly modified the D5D-T2D association. Furthermore, the inverse association of D5D with T2D was stronger among participants with a higher Cu genetic score. CONCLUSIONS:Zn and Cu status modified the relationship between FA desaturases and T2D risk. This was supported by serum Zn and Cu levels and by genetic variation related to their transport and homeostasis.

The trace elements (TEs) selenium, zinc, copper, manganese, iodine and iron are essential micronutrients that support essential metabolic functions. Imbalance in their homeostasis might contribute to the pathogenesis of major age-related chronic diseases including type 2 diabetes (T2D) and cardiovascular diseases (CVD). Emerging evidence suggests that TEs may affect health outcomes via epigenetic changes. However, few epigenome-wide association studies (EWAS) have explored TE-associated DNA methylation markers and their links to chronic disease outcomes. We conducted TE-specific exploratory EWAS using a random subcohort (n = 1030) from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort. The association between identified CpG sites and incident chronic diseases was evaluated using a case-cohort design comprising random subcohort participants and incident cases of T2D (n = 654) and CVD (n = 334). DNA methylation was measured with the MethylationEPIC BeadChip array. We used Prentice-weighted Cox proportional hazards regression models to estimate multivariable-adjusted hazard ratios (HRs) and 95

The trace elements selenium, zinc, copper, manganese, iodine, and iron are crucial for various physiological processes, including enzymatic reactions and immune responses. Dyshomeostasis of trace elements is associated with a variety of diseases including diabetes and cardiovascular diseases. It has not been clarified whether blood trace elements associate with the risk of diabetes-related vascular complications. We aimed to investigate the prospective associations between pre-diagnosis serum levels of trace elements with vascular complications in diabetes. Participants with incident diabetes and free of micro- and macrovascular disease and with pre-diagnostic serum trace element measurements from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (n = 627) were followed for microvascular and macrovascular complications (n = 212 and n = 69, respectively, median follow-up: 12.8 years). We used Cox Proportional Hazard models to investigate the associations between baseline trace element levels (per SD difference) and the risk of developing diabetes-related vascular complications. To investigate the interactions and nonlinear associations between TEs and risk of diabetes-related complications, we applied Bayesian kernel machine regression (BKMR). In multivariable models, higher iodine levels were associated with higher risk of developing total vascular complications (HR per SD, 95

The trace elements copper, iron, manganese, selenium and zinc are essential micronutrients involved in various cellular processes, all with different responsibilities. Based on that importance, their concentrations are tightly regulated in mammalian organisms. The maintenance of those levels is termed trace element homeostasis and mediated by a combination of processes regulating absorption, cellular and systemic transport mechanisms, storage and effector proteins as well as excretion. Due to their chemical properties, some functions of trace elements overlap, as seen in antioxidative defence, for example, comprising an expansive spectrum of antioxidative proteins and molecules. Simultaneously, the same is true for regulatory mechanisms, causing trace elements to influence each other's homeostases. To mimic physiological conditions, trace elements should therefore not be evaluated separately but considered in parallel. While many of these homeostatic mechanisms are well‐studied, for some elements new pathways are still discovered. Additionally, the connections between dietary trace element intake, trace element status and health are not fully unraveled, yet. With current demographic developments, also the influence of ageing as well as of certain pathological conditions is of increasing interest. Here, the TraceAge research unit was initiated, aiming to elucidate the homeostases of and interactions between essential trace elements in healthy and diseased elderly. While human cohort studies can offer insights into trace element profiles, also in vivo model organisms are used to identify underlying molecular mechanisms. This is achieved by a set of feeding studies including mice of various age groups receiving diets of reduced trace element content. To account for cognitive deterioration observed with ageing, neurodegenerative diseases, as well as genetic mutations triggering imbalances in cerebral trace element concentrations, one TraceAge work package focuses on trace elements in the murine brain, specifically the cerebellum. In that context, concentrations of the five essential trace elements of interest, copper, iron, manganese, selenium and zinc, were quantified via inductively coupled plasma‐tandem mass spectrometry, revealing differences in priority of trace element homeostasis between brain and liver. Upon moderate reduction of dietary trace element supply, cerebellar concentrations of copper and manganese deviated from those in adequately supplied animals. By further reduction of dietary trace element contents, also concentrations of cerebellar iron and selenium were affected, but not as strong as observed in liver tissue. In contrast, zinc concentrations remained stable. Investigation of aged mice revealed cerebellar accumulation of copper and iron, possibly contributing to oxidative stress on account of their redox properties. Oxidative stress affects a multitude of cellular components and processes, among them, next to proteins and lipids, also the DNA. Direct insults impairing its integrity are of relevance here, but also indirect effects, mediated by the machinery ensuring genomic stability and its functionality. The system includes the DNA damage response, comprising detection of endogenous and exogenous DNA lesions, decision on subsequent cell fate and enabling DNA repair, which presents another pillar of genomic stability maintenance. Also in proteins of this machinery, trace elements act as cofactors, shaping the hypothesis of impaired genomic stability maintenance under conditions of disturbed trace element homeostasis. To investigate this hypothesis, a variety of approaches was used, applying OECD guidelines Organisation for Economic Co‐operation and Development, adapting existing protocols for use in cerebellum tissue and establishing new methods. In order to assess the impact of age and dietary trace element depletion on selected endpoints estimating genomic instability, DNA damage and DNA repair were investigated. DNA damage analysis, in particular of DNA strand breaks and oxidatively modified DNA bases, revealed stable physiological levels which were neither affected by age nor trace element supply. To examine whether this is a result of increased repair rates, two steps characteristic for base excision repair, namely DNA incision and ligation activity, were studied. DNA glycosylases and DNA ligases were not reduced in their activity by age or trace element depletion, either. Also on the level of gene expression, major proteins involved in genomic stability maintenance were analysed, mirroring results obtained from protein studies. To conclude, the present work describes homeostatic regulation of trace elements in the brain, which, in absence of genetic mutations, is able to retain physiological levels even under conditions of reduced trace element supply to a certain extent. This is reflected by functionality of genomic stability maintenance mechanisms, illuminating the prioritization of the brain as vital organ.

Diese Dissertation untersucht essentielle Spurenelemente (TEs) im Kontext der menschlichen Gesundheit und des Alterungsprozesses, wobei der Fokus auf essentiellen TEs wie Zink (Zn), Selen (Se), Kupfer (Cu), lod (I), Eisen (Fe) und Mangan (Mn) liegt. Diese TEs sind entscheidend für die Aufrechterhaltung physiologischer Prozesse wie der Immunantwort, der antioxidativen Aktivität sowie Zellfunktionen, wobei ihre Homöostase im Körper streng reguliert ist. Störungen der TE‐Homöostase – bedingt durch Alterung, Ernährung oder andere Faktoren – können zu Stoffwechselstörungen mit potenziellen gesundheitlichen Folgen, wie beispielsweise neurodegenerative Erkrankungen führen. Die vorliegende Arbeit umfasst Humaninterventionsstudien im Rahmen der Langzeit‐Überwachung, der Biomarkerforschung und der postprandialen Serumvariabilität sowie ein in vitro ‐Modell der Blut‐Hirn‐Schranke (BHS), um die Dynamik von TEs in verschiedenen Lebensphasen und unter verschiedenen Bedingungen zu verstehen. In Kapitel 2 wurde über zwei Jahre –im Rahmen einer diätetischen Interventionsstudie im NutriAct‐Projekt– der Mineralstoffstatus einer deutschen Population mittleren Alters überwacht. Die Ergebnisse zeigten als Folge der implementierten spezifischen Ernährungsmuster signifikante Veränderungen in den Serum‐TE‐Konzentrationen, insbesondere bei Zn, Se und Mn. Die Serum‐Zn‐Konzentrationen nahmen im Laufe der Zeit signifikant ab, während die Se‐ und Mn‐Konzentrationen anstiegen. Die Ergebnisse dieser Studie deutet auf einen direkten Zusammenhang zwischen Ernährungsgewohnheiten und Serum‐Zn‐, Se‐ und Mn‐Profilen hin. Darüber hinaus bestätigte der Anstieg der Selenoprotein P (SELENOP)‐Konzentrationen im Serum erneut seine Eignung als passender Biomarker für den Se‐Status. Kapitel 3 untersucht ebenfalls die NutriAct‐Kohorte und prüft den Zusammenhang zwischen dem Schilddrüsenhormonstoffwechsel und den intrahepatischen Lipiden. In den ersten 12 Monaten der Intervention konnte ein Rückgang der Gesamt‐ und freien Triiodthyronin (T3)‐Konzentrationen sowie ein Abfall der intrahepatischen Lipide beobachtet werden. Gleichzeitig blieben die Konzentrationen des Gesamt‐ und freien Thyroxins (T4) und des Schilddrüsen‐stimulierenden Hormons (TSH) konstant, was auf einen euthyreoten Status in der repräsentativen Population hinweist. Dieses Kapitel hebt einen potenziellen Zusammenhang zwischen peripheren T3‐Konzentrationen und Leberfett hervor, was darauf hindeutet, dass der Lipidstoffwechsel durch Variationen in diesem Schilddrüsenhormon beeinflusst werden könnte, unabhängig von der Hypothalamus‐Hypophysen‐Schilddrüsen (HPT) Achse. In Kapitel 4 wurden die postprandiale Serum‐TE‐Variabilität und Bioverfügbarkeit bei jungen und älteren Probanden in der BioMiEL‐Studie untersucht. Es wurden altersbedingte Unterschiede in den Ausgangsserumkonzentrationen von Zn, Se und Cu festgestellt, wobei ältere Teilnehmer höhere Serum‐Cu‐ und Se‐Konzentrationen, aber niedrigere Zn‐Konzentrationen aufwiesen, was in einem erhöhten Cu/Zn‐Verhältnis resultierte. Während postprandiale Änderungen in den Serum‐TE‐Konzentrationenn generell begrenzt waren, wurden einige Variationen bei Cu, Se und I beobachtet, die Unterschiede im TE‐Stoffwechsel zwischen den Altersgruppen widerspiegeln könnten. Insbesondere Zn zeigte starke zeitabhängige Schwankungen, was auf seine Sensibilität gegenüber postprandialen Veränderungen hinweist. Im Gegensatz dazu blieb die freie Zn‐Fraktion im Serum weitgehend unverändert, was auf einen kompensatorischen Mechanismus hindeutet, der unabhängig von der postprandialen Variabilität der gesamten Serum‐Zn‐Konzentrationen ist. Kapitel 5 befasst sich mit dem Se‐Status von Veganern, einer Gruppe, die aufgrund diätetischer Einschränkungen einem Se‐Mangelrisiko ausgesetzt ist. Durch gezielte diätetische Interventionen, einschließlich der Se‐Supplementierung oder des täglichen Verzehrs von Paranussmus, wurden innerhalb von zwei Wochen signifikante Anstiege der Serum‐Se‐Konzentrationen und der SELENOP‐Konzentrationen beobachtet. Diese Ergebnisse unterstreichen die Bedeutung diätetischer Se‐Quellen für die Verbesserung des Se‐Status, insbesondere bei Bevölkerungsgruppen, die sich pflanzenbasiert ernähren. In Kapitel 6 wurde ein Modell bestehend aus Gehirnendothelzellen des Schweins (PBCEC) verwendet, um den Zn‐modulierten bidirektionalen Cu‐Transfer über die BHS zu untersuchen. Das Zellkultursystem der BHS spiegelt die in vivo ‐Bedingungen des Cu‐ und Zn‐Transports wider, wobei Cu während einer 48‐stündigen Inkubationsperiode von der Blutseite (apikal) auf die Gehirnseite (basolateral) übertragen wurde. Die Co‐Inkubation mit Zn führte zu einem reduzierten Cu/Zn‐Verhältnis (< 1) auf der apikalen Seite, was den Cu‐Transfer über die BHS hemmte oder verlangsamte. Dies könnte auf eine erhöhte intrazelluläre Sequestrierung von Cu durch Metallothionein (MT) zurückzuführen sein, einem Protein, dessen Expression durch die Verfügbarkeit von Zn hochreguliert wird. Für den umgekehrten Cu‐Transfer wurde keine solche Hemmung durch Zn beobachtet, was darauf hindeutet, dass BHS‐Endothelzellen möglicherweise dazu beitragen könnten, erhöhte Cu‐Konzentrationen im Gehirn zu reduzieren. Bemerkenswerterweise zeigte Zn selbst keinen signifikanten Transfer zwischen den Kompartimenten, was lediglich auf einen minimalen Austausch über die BHS hinweist. Darüber hinaus blieb die Integrität der BHS unter den verschiedenen Inkubationsbedingungen unbeeinflusst. Diese Dissertation unterstreicht die Bedeutung des Verständnisses der TE‐Dynamik in Bezug auf die Ernährung und das Altern. Sie hebt das Potenzial diätetischer Interventionen zur Verbesserung des TE‐Status hervor, insbesondere hinsichtlich eines Se‐Mangels für gefährdete Gruppen wie Veganer oder ältere Menschen, und betont den Bedarf an weiterer Forschung zu den Interaktionen verschiedener TEs und deren Auswirkungen auf Stoffwechsel‐ und neurodegenerative Erkrankungen. Um den TE‐Status vollständig bewerten zu können, ist es unerlässlich, robuste Methoden sowie ein umfassendes Spektrum an Biomarkern des TE‐Status einzusetzen. Dieser Ansatz gewährleistet eine genauere Beurteilung der TE‐Homöostase und trägt zur Optimierung von Interventionen bei, die auf altersbedingte, ernährungsbedingte oder auch synergistisch bedingte TE‐Defizite abzielen.

A vegan diet is associated with health benefits but may also lead to inadequate intake of essential nutrients. Due to the lower selenium content in plant-based compared to animal-based foods, many vegans do not reach the recommended selenium intake in Europe. The only plant-based food with high selenium content is the Brazil nut, even though there is also a high variability. Therefore, we investigated the effectiveness of Brazil nut butter compared to a dietary supplement as selenium source to improve the selenium status of vegans and omnivores. 44 vegans and 42 omnivores were randomly assigned to one of three intervention groups, either receiving placebo or consuming additional 55 µg of selenium daily as Brazil nut butter or supplement for two weeks. Serum selenium concentrations, glutathione peroxidase 3 (GPX3), and selenoprotein P (SELENOP) were measured at baseline and after intervention. Additionally, dietary selenium intake was estimated using a five-day dietary protocol. The estimated selenium intake was significantly lower in vegans compared to omnivores and correlated with all three selenium biomarkers. Independent of the dietary pattern (vegan or omnivore), Brazil nut butter as well as supplement significantly increased serum selenium and SELENOP concentrations, while there were no changes in the placebo groups. Both interventions were equally effective in increasing selenium levels, but the upregulation of SELENOP was more pronounced in vegans than in omnivores. Brazil nuts are a plant-based source of selenium suitable for vegans and omnivores to improve their selenium status when consumed once in a while. Clinical trials registration number: NCT05814874, April 18 2023.

LebensmittelchemieVolume 78, Issue S1 p. S1-089-S1-089 Abstract Assessing Combined Metal Exposure: Insights into Cellular Bioavailability, Oxidative Stress, and Toxicity Mechanisms of Co(II) and Ni(II) in HepG2 Cells Alicia Thiel, Alicia Thiel Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, GermanySearch for more papers by this authorVivien Michaelis, Vivien Michaelis Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, GermanySearch for more papers by this authorMartin Simon, Martin Simon Molecular Cell Biology and Microbiology, Faculty of Mathematics and Natural Sciences, University of Wuppertal, GermanySearch for more papers by this authorTanja Schwerdtle, Tanja Schwerdtle German Federal Institute for Risk Assessment (BfR), Berlin, Germany TraceAge – DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly (FOR 2558), Berlin-Potsdam-Jena-WuppertalSearch for more papers by this authorJulia Bornhorst, Corresponding Author Julia Bornhorst [email protected] Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Germany TraceAge – DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly (FOR 2558), Berlin-Potsdam-Jena-Wuppertal[email protected]Search for more papers by this author Alicia Thiel, Alicia Thiel Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, GermanySearch for more papers by this authorVivien Michaelis, Vivien Michaelis Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, GermanySearch for more papers by this authorMartin Simon, Martin Simon Molecular Cell Biology and Microbiology, Faculty of Mathematics and Natural Sciences, University of Wuppertal, GermanySearch for more papers by this authorTanja Schwerdtle, Tanja Schwerdtle German Federal Institute for Risk Assessment (BfR), Berlin, Germany TraceAge – DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly (FOR 2558), Berlin-Potsdam-Jena-WuppertalSearch for more papers by this authorJulia Bornhorst, Corresponding Author Julia Bornhorst [email protected] Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Germany TraceAge – DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly (FOR 2558), Berlin-Potsdam-Jena-Wuppertal[email protected]Search for more papers by this author First published: 01 March 2024 https://doi.org/10.1002/lemi.202452066AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume78, IssueS1Supplement: Abstracts der Vorträge der Regionalverbände und die der Posterflashtalks der AG JLCMarch/April 2024Pages S1-089-S1-089 RelatedInformation

The European Commission asked EFSA to update its 2009 risk assessment on arsenic in food carrying out a hazard assessment of inorganic arsenic (iAs) and using the revised exposure assessment issued by EFSA in 2021. Epidemiological studies show that the chronic intake of iAs via diet and/or drinking water is associated with increased risk of several adverse outcomes including cancers of the skin, bladder and lung. The CONTAM Panel used the benchmark dose lower confidence limit based on a benchmark response (BMR) of 5% (relative increase of the background incidence after adjustment for confounders, BMDL05) of 0.06 μg iAs/kg bw per day obtained from a study on skin cancer as a Reference Point (RP). Inorganic As is a genotoxic carcinogen with additional epigenetic effects and the CONTAM Panel applied a margin of exposure (MOE) approach for the risk characterisation. In adults, the MOEs are low (range between 2 and 0.4 for mean consumers and between 0.9 and 0.2 at the 95th percentile exposure, respectively) and as such raise a health concern despite the uncertainties.