Biomonitoring of deoxynivalenol and deoxynivalenol-3-glucoside in human volunteers : renal excretion profiles

Biomarkers for the determination of the dietary exposure to deoxynivalenol (DON) have been proposed in the past but so far no quantification of their use in humans has been carried out. Following a human intervention study with two mycotoxins, namely DON and deoxynivalenol-3-glucoside (DON3G), the renal excretion of these compounds, including their phase II metabolites, was analysed. The purpose was to develop biokinetic models that can be used to determine: (1) the preferred (set of) urinary biomarker(s), (2) the preferred urinary collection period, and (3) a method to estimate the dietary exposure to these mycotoxins. Twenty adult volunteers were restricted in consuming cereals and cereal-based foods for 4 days. At day 3, a single dose of 1 mu g/kg body weight of DON or DON3G was orally administered to 16 volunteers; 4 volunteers served as control. All individual urine discharges were collected during 24 h after administration. The metabolism and renal excretion could be described by a biokinetic model using three physiological compartments (gastrointestinal tract, liver, and kidneys). Kinetic analysis revealed a complete recovery of the renal excretion of total DON (mainly DON and its glucuronides) within 24 h after administration of DON or DON3G. The so-called 'reverse dosimetry' factor was used to determine the preferred (set of) biomarker(s) and to estimate the dietary intake of the parent compounds in the future. The fact that DON3G was absorbed and mainly excreted as DON and its glucuronides confirms that DON3G (as well as other modified forms) should be taken into account in the exposure and risk assessment of this group of mycotoxins

Plan for development of case studies - Deliverable Report AD 15.1 WP 15 - Mixtures, HBM and human health risk

This deliverable describes the activities in task 15.3 leading up to the development of cases studies for mixture health effects and outlines the proposed case studies. The proposed case studies are: · Developmental neurotoxicity beyond polybrominated diphenylethers · Heavy metals and nephrotoxicity · Anti-androgenic chemicals and male reproductive health · Chromium (VI), nickel and polycyclic aromatic hydrocarbons and lung cancer · Addressing exposure misclassification in mixture studies The Addendum provides further details about multi-year perspective and timing, as well as detailed budgetary aspects per case study.HBM4EU- Grant agreement 733032 HORIZON2020 Programmeinfo:eu-repo/semantics/publishedVersio

Biomarkers of effect as determined in human biomonitoring studies on hexavalent chromium and cadmium in the period 2008–2020

This research was supported by funding from the European Union's Horizon 2020 research and innovation Programme under grant agreement No 733032 HBM4EU.A number of human biomonitoring (HBM) studies have presented data on exposure to hexavalent chromium [Cr (VI)] and cadmium (Cd), but comparatively few include results on effect biomarkers. The latter are needed to identify associations between exposure and adverse outcomes (AOs) in order to assess public health implications. To support improved derivation of EU regulation and policy making, it is of great importance to identify the most reliable effect biomarkers for these heavy metals that can be used in HBM studies. In the framework of the Human Biomonitoring for Europe (HBM4EU) initiative, our study aim was to identify effect biomarkers linking Cr(VI) and Cd exposure to selected AOs including cancer, immunotoxicity, oxidative stress, and omics/epigenetics. A comprehensive PubMed search identified recent HBM studies, in which effect biomarkers were examined. Validity and applicability of the markers in HBM studies are discussed. The most frequently analysed effect biomarkers regarding Cr(VI) exposure and its association with cancer were those indicating oxidative stress (e.g., 8-hydroxy-2 & rsquo;-deoxyguanosine (8-OHdG), malondialdehyde (MDA), glutathione (GSH)) and DNA or chromosomal damage (comet and micronucleus assays). With respect to Cd and to some extent Cr, 0-2-microglobulin (B2-MG) and N-acetyl-0-D-glucosaminidase (NAG) are well-established, sensitive, and the most common effect biomarkers to relate Cd or Cr exposure to renal tubular dysfunction. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule (KIM)-1 could serve as sensitive biomarkers of acute kidney injury in response to both metals, but need further investigation in HBM studies. Omics-based biomarkers, i.e., changes in the (epi-)genome, transcriptome, proteome, and metabolome associated with Cr and/or Cd exposure, are promising effect biomarkers, but more HBM data are needed to confirm their significance. The combination of established effect markers and omics biomarkers may represent the strongest approach, especially if based on knowledge of mechanistic principles. To this aim, also mechanistic data were collected to provide guidance on the use of more sensitive and specific effect biomarkers. This also led to the identification of knowledge gaps relevant to the direction of future research.European Commission 733032 HBM4E

lessons learned and future trends

Funding Information: Thanks are due to CESAM (UIDP/50017/2020+UIDB/50017/2020+LA/P/0094/2020), and ToxOmics (UIDB/00009/2020; UIDP/00009/2020), through national funds. L.B. thanks Research Infrastructure RECETOX RI (No. LM2018121), financed by the Ministry of Education, Youth and Sports, and the project CETOCOEN EXCELLENCE (No. CZ.02.1.01/0.0/0.0/17_043/0009632) for a supportive background of the European Union’s Horizon 2020 research and innovation program under grant agreement No. 857560, and to the HBM4EU, under grant agreement No. 733032. This publication reflects only the authors’ view and the European Commission is not responsible for any use that may be made of the information it contains. Funding Information: This study was co-funded by the HBM4EU, which has received funding from the European Union’s research and innovation programme Horizon 2020 under grant agreement No. 733032, and from the authors’ institutions. Publisher Copyright: © 2022 by the authors.Mycotoxins are natural metabolites produced by fungi that contaminate food and feed worldwide. They can pose a threat to human and animal health, mainly causing chronic effects, e.g., immunotoxic and carcinogenic. Due to climate change, an increase in European population exposure to mycotoxins is expected to occur, raising public health concerns. This urges us to assess the current human exposure to mycotoxins in Europe to allow monitoring exposure and prevent future health impacts. The mycotoxins deoxynivalenol (DON) and fumonisin B1 (FB1) were considered as priority substances to be studied within the European Human Biomonitoring Initiative (HBM4EU) to generate knowledge on internal exposure and their potential health impacts. Several policy questions were addressed concerning hazard characterization, exposure and risk assessment. The present article presents the current advances attained under the HBM4EU, research needs and gaps. Overall, the knowledge on the European population risk from exposure to DON was improved by using new harmonised data and a newly derived reference value. In addition, mechanistic information on FB1 was, for the first time, organized into an adverse outcome pathway for a congenital anomaly. It is expected that this knowledge will support policy making and contribute to driving new Human Biomonitoring (HBM) studies on mycotoxin exposure in Europe.publishersversionpublishe

Current Advances, Research Needs and Gaps in Mycotoxins Biomonitoring under the HBM4EU-Lessons Learned and Future Trends

ReviewThis article belongs to the Special Issue Human Biomonitoring and Risk Assessment of Mycotoxins.Mycotoxins are natural metabolites produced by fungi that contaminate food and feed worldwide. They can pose a threat to human and animal health, mainly causing chronic effects, e.g., immunotoxic and carcinogenic. Due to climate change, an increase in European population exposure to mycotoxins is expected to occur, raising public health concerns. This urges us to assess the current human exposure to mycotoxins in Europe to allow monitoring exposure and prevent future health impacts. The mycotoxins deoxynivalenol (DON) and fumonisin B1 (FB1) were considered as priority substances to be studied within the European Human Biomonitoring Initiative (HBM4EU) to generate knowledge on internal exposure and their potential health impacts. Several policy questions were addressed concerning hazard characterization, exposure and risk assessment. The present article presents the current advances attained under the HBM4EU, research needs and gaps. Overall, the knowledge on the European population risk from exposure to DON was improved by using new harmonised data and a newly derived reference value. In addition, mechanistic information on FB1 was, for the first time, organized into an adverse outcome pathway for a congenital anomaly. It is expected that this knowledge will support policy making and contribute to driving new Human Biomonitoring (HBM) studies on mycotoxin exposure in Europe.This study was co-funded by the HBM4EU, which has received funding from the European Union’s research and innovation programme Horizon 2020 under grant agreement No. 733032, and from the authors’ institutions. Thanks are due to CESAM(UIDP/50017/2020+UIDB/50017/2020+LA/P/0094/2020), and ToxOmics (UIDB/00009/2020; UIDP/00009/2020), through national funds. L.B. thanks Research Infrastructure RECETOX RI (No. LM2018121), financed by the Ministry of Education, Youth and Sports, and the project CETOCOEN EXCELLENCE (No. CZ.02.1.01/0.0/0.0/17_043/0009632) for a supportive background of the European Union’s Horizon 2020 research and innovation program under grant agreement No. 857560, and to the HBM4EU, under grant agreement No. 733032.info:eu-repo/semantics/publishedVersio

ANTIGUA PILA BAUTISMAL [Material gráfico]

FOTO PAPEL DE PILA BAUTISMALPILA DONDE BAUTIZARON A LOS MENCEYES GUANCHES. ADQUIRIDA POR EL COLECCIONISTA EN TENERIFE.Copia digital. Madrid : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 201

Safety evaluation of the food enzyme containing cellulase, endo-1,3(4)-beta-glucanase and endo-1,4-beta-xylanase activities from the non-genetically modified Trichoderma reesei strain AR-256

[EN] The food enzyme containing cellulase (EC 3.2.1.4), endo-1,3(4)-beta-glucanase (EC 3.2.1.6) and endo-1,4-beta-xylanase (EC 3.2.1.8) is produced with the non-genetically modified Trichoderma reesei strain AR-256 by AB-Enzymes GmbH. The food enzyme is considered free from viable cells of the production organism. It is intended to be used in seven food manufacturing processes: baking processes, cereal-based processes, brewing processes, fruit and vegetable processing for juice production, wine and wine vinegar production, distilled alcohol production and grain treatment for production of starch and gluten fractions. Since the residual amounts of total organic solids (TOS) are removed during grain treatment and distilled alcohol production, dietary exposure was estimated for the remaining five processes and amounted up to 3.92 mg TOS/kg body weight (bw) per day. The toxicity studies were carried out with an endo-1,4-beta-xylanase from T. reesei, considered by the Panel as a suitable substitute, because the genetic differences between the strains are well characterised and of no concern. Additionally, several strains derived from the production strain are considered safe by EFSA and the manufacturing of both food enzymes is similar. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by a repeated dose 90-day oral toxicity rat study. The no observed adverse effect level of 939 mg TOS/kg bw per day, the highest dose tested, compared with the estimated dietary exposure, resulted in a margin of exposure above 239. In the search for the similarity of the amino acid sequences to known allergens, one match (salmon) was found. The Panel considered that, under the intended conditions of use (except distilled alcohol production), the risk of allergic reactions by dietary exposure cannot be excluded, in particular for individuals sensitised to salmon. The Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use.The Panel wishes to thank the following for the support provided to this scientific output: Erik Boinowitz and Helen Regina.Lambré, C.; Barat Baviera, JM.; Bolognesi, C.; Cocconcelli, PS.; Crebelli, R.; Gott, DM.; Grob, K.... (2022). Safety evaluation of the food enzyme containing cellulase, endo-1,3(4)-beta-glucanase and endo-1,4-beta-xylanase activities from the non-genetically modified Trichoderma reesei strain AR-256. EFSA Journal. 20(12):1-18. https://doi.org/10.2903/j.efsa.2022.7676118201

Safety assessment of the process Poly Recycling, based on the VACUNITE (EREMA basic and Polymetrix SSP V-leaN) technology, used to recycle post-consumer PET into food contact materials

[EN] The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the recycling process Poly Recycling (EU register number RECYC262), which uses the VACUNITE (EREMA basic and Polymetrix SSP V-leaN) technology. The input is and dried poly(ethylene terephthalate) (PET) flakes mainly originating from collected post-consumer PET containers, including no more than 5% PET from non-food consumer applications. The flakes are pre-decontaminated in a first reactor at under before being extruded and pelletised. The pellets are crystallised, preheated and then submitted to solid-state polycondensation (SSP) in a continuous reactor at under and. Having examined the challenge test provided, the Panel concluded that the reactor (step 2), preheater (step 4) and the SSP reactor (step 5) are critical in determining the decontamination efficiency of the process. The operating parameters to control the performance are temperature, pressure and residence time for steps 2, 4 and 5 as well as gas velocity for steps 4 and 5. It was demonstrated that this recycling process is able to ensure that the level of migration of potential unknown contaminants into food is below the conservatively modelled migration of 0.1 lg/kg food. Therefore, the Panel concluded that the recycled PET obtained from this process is not of safety concern, when used at up to 100% for the manufacture of materials and articles for contact with all types of foodstuffs, including drinking water, for long-term storage at room temperature, with or without hotfill. Articles made of this recycled PET are not intended to be used in microwave and conventional ovens and such uses are not covered by this evaluationThe [Panel or Scientific Committee or EFSA] wishes to thank the following for the support provided to this scientific output: [staff members or others who made a contribution but are not eligible as authors]. The Panel [Panel/Scientific Committee/EFSA] wishes to acknowledge all European competent institutions, Member State bodies and other organisations that provided data for this scientific output.Lambré, C.; Barat Baviera, JM.; Bolognesi, C.; Chesson, A.; Cocconcelli, PS.; Crebelli, R.; Gott, DM.... (2022). Safety assessment of the process Poly Recycling, based on the VACUNITE (EREMA basic and Polymetrix SSP V-leaN) technology, used to recycle post-consumer PET into food contact materials. EFSA Journal. 20(12):1-14. https://doi.org/10.2903/j.efsa.2022.7652114201

Safety evaluation of the food enzyme triacylglycerol lipase from the genetically modified Aspergillus niger strain NZYM-DB

[EN] The food enzyme triacylglycerol lipase (triacylglycerol acylhydrolase EC 3.1.1.3) is produced with a genetically modified Aspergillus niger strain NZYM-DB by Novozymes A/S. The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and recombinant DNA. The food enzyme is intended to be used in an immobilised form in the production of modified fats and oils by interesterification. Based on the estimated use levels recommended for interesterification of fats and oils and individual data from the EFSA Comprehensive European Food Database, dietary exposure to the food enzyme-total organic solids (TOS) was estimated to be up to 0.75 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not raise a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level at the highest dose of 1,132 mg TOS/kg bw per day, which when compared with the estimated dietary exposure, results in a margin of exposure of at least 1,500. Similarity of the amino acid sequence to those of known allergens was searched and no match was found. The Panel considered that, under the intended conditions of use, the risk of allergic sensitisation and elicitation reactions by dietary exposure cannot be excluded, but the likelihood of such reactions to occur is likely to be low. Based on the data provided, the immobilisation of the food enzyme and the removal of total organic solids during fats and oils processing, the Panel concluded that the food enzyme does not give rise to safety concerns under the intended conditions of use.Silano, V.; Barat Baviera, JM.; Bolognesi, C.; Cocconcelli, PS.; Crebelli, R.; Gott, DM.; Grob, K.... (2021). Safety evaluation of the food enzyme triacylglycerol lipase from the genetically modified Aspergillus niger strain NZYM-DB. EFSA Journal. 19(1):1-16. https://doi.org/10.2903/j.efsa.2021.6366S11619

Safety assessment of the process Bangladesh Petrochemical Company, based on the Vacurema Prime technology, used to recycle post-consumer PET into food contact materials

[EN] The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP Panel) assessed the safety of the recycling process Bangladesh Petrochemical Company (EU register number RECYC246), which uses the Vacurema Prime technology. The input material is hot caustic washed and dried poly (ethylene terephthalate) (PET) flakes originating from collected post-consumer PET containers, including no more than 5% PET from non-food applications. The flakes are heated in a batch reactor (step 2) and then heated in a continuous reactor (step 3) before being extruded into pellets. Having examined the challenge test provided, the Panel concluded that step 2 and step 3 are critical in determining the decontamination efficiency of the process. The operating parameters to control the performance of these steps are temperature, pressure and residence time. The Panel concluded that this recycling process is able to ensure that the level of migration of potential unknown contaminants into food is below the conservatively modelled migration of 0.1 mu g/kg food. Therefore, the recycled PET obtained from this process is not of safety concern, when used at up to 100% for the manufacture of materials and articles for contact with all types of foodstuffs for long-term storage at room temperature, with or without hotfill. The final articles made of this recycled PET are not intended to be used in microwave and conventional ovens and such uses are not covered by this evaluation.Lambré, C.; Barat Baviera, JM.; Bolognesi, C.; Chesson, A.; Cocconcelli, PS.; Crebelli, R.; Gott, DM.... (2022). Safety assessment of the process Bangladesh Petrochemical Company, based on the Vacurema Prime technology, used to recycle post-consumer PET into food contact materials. EFSA Journal. 20(6):1-14. https://doi.org/10.2903/j.efsa.2022.736011420