Article
Agriculture, Multidisciplinary
Florian Kaltner
Summary: Toxic plant alkaloids (TPAs) found in food may be affected by storing or processing, leading to decreased levels of the parent alkaloids. However, little is known about potential transformation products and their toxic potential. This perspective summarizes the current knowledge on the behavior of opium, pyrrolizidine, and tropane alkaloids during processing or storing, and highlights analytical strategies to identify and elucidate potential transformation products.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Review
Plant Sciences
Jacqueline Wiesner
Summary: The toxicity of plants containing certain pyrrolizidine alkaloids has been recognized for a long time, leading to regulatory action on herbal medicinal products. In addition to the plants themselves, contamination from accessory herbs has been identified, leading to limits being set for all herbal medicinal products by regulatory authorities.
Article
Food Science & Technology
Anne-Margarethe Enge, Florian Kaltner, Christoph Gottschalk, Angelina Kin, Michael Kirstgen, Joachim Geyer, Anja These, Helen Hammer, Oliver Poetz, Albert Braeuning, Stefanie Hessel-Pras
Summary: This study investigates the transporter-mediated uptake of PAs and its implications in PA toxicity, finding that treatment with PAs affects transporter expression levels in HepaRG cells. Knockdown of the two uptake transporters results in reduced PA uptake and attenuated cytotoxic effects of PAs in a time-dependent manner. The results confirm the importance of toxicokinetic studies for the risk assessment of PAs.
MOLECULAR NUTRITION & FOOD RESEARCH
(2022)
Article
Chemistry, Applied
Haolei Han, Changling Jiang, Chen Wang, Yuting Lu, Ziqi Wang, Yunfeng Chai, Xiangchun Zhang, Xin Liu, Chengyin Lu, Hongping Chen
Summary: This study investigated the dissipation pattern and conversion behavior of PAs/PANOs during tea manufacturing and brewing using ultra high-performance liquid chromatography tandem mass spectrometry. The results showed that PANOs had higher degradation rates than PAs during tea manufacturing, and drying played a key role in PANOs degradation. Additionally, PANOs could be converted to corresponding PAs, and higher transfer rates of PANOs were observed during tea brewing compared to PAs.
Article
Food Science & Technology
Natalia Casado, Sonia Morante-Zarcero, Isabel Sierra
Summary: This review provides an overview of pyrrolizidine alkaloids (PAs), including their chemical structure, classification, toxicity, risk assessment, occurrence in food, contamination paths, and the effect of food processing. PAs have been found to exhibit various toxicities, and it is important to develop sensitive analytical methods to control their occurrence in food. Although maximum concentration limits have been regulated, further research is needed to improve the risk management of these alkaloids and assess the real intake by the population.
TRENDS IN FOOD SCIENCE & TECHNOLOGY
(2022)
Review
Chemistry, Multidisciplinary
Natalia Casado, Gema Casado-Hidalgo, Lorena Gonzalez-Gomez, Sonia Morante-Zarcero, Isabel Sierra
Summary: Pyrrolizidine alkaloids, tropane alkaloids, and opium alkaloids are natural plant toxins that are of great concern in food safety due to their presence in various foods and feeds. Despite recent legislation, the concentration levels of these toxins often exceed the maximum limits established by authorities. Moreover, the regulations primarily focus on raw materials and do not consider processed products. Therefore, it is crucial to assess the health risk associated with these alkaloids through diet. This review aims to provide insight into these alkaloids and their influence on content and stability during food processing and culinary preparation, highlighting the need for further research to understand their transformation and determine the exact risk exposure to the population.
APPLIED SCIENCES-BASEL
(2023)
Article
Biochemistry & Molecular Biology
Julia Buchmueller, Florian Kaltner, Christoph Gottschalk, Maria Maares, Albert Braeuning, Stefanie Hessel-Pras
Summary: This study aims to elucidate the toxicokinetic parameters of PAs, including their uptake and metabolism, using in vitro models. The results show that PAs pass through the intestinal barrier and reach the liver, where they are metabolized into reactive metabolites that interact with nucleophilic centers. These findings contribute to a better understanding of the molecular processes underlying the observed effects of PAs in vivo.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Josephin Gluck, Julia Waizenegger, Albert Braeuning, Stefanie Hessel-Pras
Summary: Pyrrolizidine alkaloids (PAs) are secondary metabolites produced by plants as a defense mechanism, but human exposure through contaminated food can lead to liver toxicity, prompting the need for further research on their effects on cells. Different structurally PAs have been found to induce varying cytotoxic effects in human hepatoma cells, highlighting a strong structure-activity relationship that requires further investigation into their apoptotic mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Food Science & Technology
Yueyang Pan, Jiang Ma, Hui Zhao, Peter P. Fu, Ge Lin
Summary: Pyrrolizidine alkaloids (PAs) are plant toxins that can be found in approximately 6000 plant species. Consuming PA-contaminated or PA-containing foodstuffs, herbs, or supplements can pose a potential threat to human health. Different regulatory authorities have established different acceptable limits for PAs, assuming equal hepatotoxic potency despite their structural diversity. This study used a zebrafish model to evaluate the hepatotoxic potency of different PAs and explore the physiological pathways involved in PA-induced liver toxicity. The results showed distinct structure-dependent hepatotoxicity and identified the involvement of inflammation, apoptosis, and steatosis in PA-induced liver toxicity.
FOOD AND CHEMICAL TOXICOLOGY
(2023)
Review
Biochemical Research Methods
Barbara Steinhoff
Summary: This review provides an overview of the legal requirements for testing potential contaminants in herbal drugs, including pesticide residues, heavy metals, microbiological purity, aflatoxins, and polycyclic aromatic hydrocarbons. It also discusses the decrease of pyrrolizidine alkaloids in herbal drugs over the past few years, while acknowledging that the issue cannot be completely solved in the near future.
PHYTOCHEMICAL ANALYSIS
(2021)
Article
Biochemistry & Molecular Biology
Elena Stefova, Marinela Cvetanoska, Jane Bogdanov, Vlado Matevski, Jasmina Petreska Stanoeva
Summary: A systematic study was conducted to investigate the extraction efficiency of pyrrolizidine alkaloids (PAs) and pyrrolizidine alkaloid N-oxides (PANOs) from plant material for LC/MS analysis. Methanol extraction with a single clean-up step using SPE C18 column was found to be the optimal method. LC-ESI-MS/MS analysis revealed the distribution and diversity of PAs and PANOs in plant material from various Boraginaceae species. Qualitative and quantitative analyses showed the profiles of 1,2-unsaturated PAs in each sample and estimated their toxic potential. This method can be used for monitoring the presence of these secondary metabolites in the food chain for risk management purposes.
CHEMISTRY & BIODIVERSITY
(2022)
Review
Plant Sciences
Barbara Steinhoff
Summary: In response to potential contamination of medicinal plant materials with pyrrolizidine alkaloids from weeds, suppliers and manufacturers have established measures to monitor and collect data. The results show a significant reduction in pyrrolizidine alkaloid burden in herbal drugs and extracts, indicating the effectiveness of implemented measures in reducing contamination.
Article
Food Science & Technology
Begona Fernandez-Pintor, Natalia Casado, Sonia Morante-Zarcero, Isabel Sierra
Summary: Pyrrolizidine alkaloids (PAs) have attracted attention in food safety due to their potential health risk. Tea and herbal tea, as they can be contaminated with PAs-producing weeds, have been particularly highlighted. This study simulated the cross-contamination of chamomile tea samples with weeds to evaluate the effect of brewing on PA content. The results showed that PAs are stable compounds and the initial PA concentration strongly affects their thermal stability. Not all PAs are effectively transferred from dry material to the infusion during brewing, and the extraction efficiency may be influenced by the type of weed. The study emphasizes the importance of analyzing infusion samples to correctly assess the risk exposure of consumers to PAs.
Article
Biochemistry & Molecular Biology
Anne-Margarethe Enge, Florian Kaltner, Christoph Gottschalk, Albert Braeuning, Stefanie Hessel-Pras
Summary: The study focused on evaluating the general mode of action of PA transport in the human hepatoma cell line HepaRG, using seven structurally different PAs. Results indicated that PAs are taken up into HepaRG cells in a predominantly active and structure-dependent manner, which correlates with other experimental endpoints such as cytotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Food Science & Technology
Julia Waizenegger, Josephin Glueck, Marcus Henricsson, Claudia Luckert, Albert Braeuning, Stefanie Hessel-Pras
Summary: The study found that PAs downregulate the expression of genes related to bile acid synthesis and transport in human liver cells, potentially leading to progressive impairment of bile acid homeostasis and accumulation of toxic bile acids. Additionally, important biliary efflux mechanisms are disturbed due to PA exposure, which may play a role in the development of severe liver damage in humans intoxicated with PAs.
Article
Food Science & Technology
Wilma Taverne-Veldhuizen, Ron Hoogenboom, Guillaume ten Dam, Rik Herbes, Vincenzo Fogliano, Pieternel Luning
Summary: This study investigated the impact of hydrogenation on dioxins in palm oil products. The toxic equivalent (TEQ) levels of dioxins varied with different degrees of hydrogenation, and optimization of the process is needed to reduce the risk of exceeding dioxin limits.
Article
Food Science & Technology
Maryam Zare Jeddi, Polly E. Boon, Francesco Cubadda, Ron Hoogenboom, Hans Mol, Hans Verhagen, Dick T. H. M. Sijm
Summary: This paper discusses the role and challenges of dietary exposure sciences in the field of food safety and nutrition, particularly in the European context. It emphasizes the importance of timely and accurate assessment of the impact of changes in food systems on consumer's and public health.
TRENDS IN FOOD SCIENCE & TECHNOLOGY
(2022)
Article
Chemistry, Applied
Felicia Akuamoa, Toine F. H. Bovee, Ruud van Dam, Lilian Maro, Sebastiaan Wesseling, Jacques Vervoort, Ivonne M. C. M. Rietjens, Ron L. A. P. Hoogenboom
Summary: The use of herbal supplements for improved sexual performance is popular in Ghana, but the high rate of adulteration compromises their safety. A study analyzed 40 herbal supplements and found significant amounts of sildenafil, vardenafil, and tadalafil in many of them. The study highlights the importance of a tiered approach combining bioassays and chemical analysis to identify unknown bioactive compounds.
FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT
(2022)
Article
Food Science & Technology
Laurent Bodin, Jesus del Mazo, Bettina Grasl-Kraupp, Christer Hogstrand, Jean-Charles Leblanc, Margherita Bignami, Laurentius (Ron) Hoogenboom, Carlo Stefano Nebbia, Elsa Nielsen, Evangelia Ntzani, Annette Petersen, Dieter Schrenk, Christiane Vleminckx, Heather Wallace, Andreas Focks, Ales Gregorc, Manfred Metzler, Fabio Sgolastra, Simone Tosi, Zsuzsanna Horvath, Alessio Ippolito, Agnes Rortais, Hans Steinkellner, Csaba Szentes, Salomon Sand
Summary: The European Commission has requested the EFSA to assess the risk of hydroxymethylfurfural (HMF) in honey bee feed on animal health. HMF has low acute toxicity but causes increased mortality with chronic exposure. Based on a 20-day study, a benchmark dose lower limit 10% (BMDL10) of 1.16 μg HMF per bee per day has been established. Additional reference points were calculated for different exposure durations. Analysis of HMF concentrations in bee feed from EU Member States and the industry showed that exposure levels were well below the BMDL10, indicating no concern. However, with long-term exposure, there was a risk to bee health.
Article
Toxicology
Aafke W. F. Janssen, Jochem Louisse, Deborah Rijkers, Nicole E. T. Pinckaers, Sjoerdtje A. Hoekstra, Ron L. A. P. Hoogenboom, Ad A. C. M. Peijnenburg, Karsten Beekmann
Summary: This study investigates the effects of per- and polyfluoroalkyl substances (PFASs) on B cells and identifies the decreased expression of RAG1 and RAG2 as potential targets in the immunotoxicity of PFASs. The concentration-response modeling analysis indicates that PFNA has the highest potency in inducing immunotoxic effects among the studied PFASs (PFNA > PFOA > PFOS > PFHxS).
ARCHIVES OF TOXICOLOGY
(2023)
Article
Agriculture, Multidisciplinary
Daria Savvateeva, Britta Ohlhoff, Ron L. A. P. Hoogenboom, Robert Pieper, Jorge Numata
Summary: This study presents toxicokinetic models for the transfer of non-dioxin-like polychlorinated biphenyls (ndl-PCBs) into chicken eggs and meat, improving the prediction of experimental data. The study also calculates the highest level of ndl-PCBs in laying hen feed to ensure safety in meat and eggs, considering the possibility of soil contamination.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Food Science & Technology
Dieter Schrenk, Margherita Bignami, Laurent Bodin, James Kevin Chipman, Jesus del Mazo, Bettina Grasl-Kraupp, Christer Hogstrand, Jean-Charles Leblanc, Elsa Nielsen, Evangelia Ntzani, Annette Petersen, Salomon Sand, Tanja Schwerdtle, Christiane Vleminckx, Heather Wallace, Sven Daenicke, Carlo Stefano Nebbia, Isabelle P. Oswald, Elena Rovesti, Hans Steinkellner, Laurentius (Ron) Hoogenboom
Summary: In 2018, the EFSA CONTAM Panel conducted an evaluation of the risks posed by fumonisins in animal feed, establishing no observed adverse effect levels for pigs, poultry, and horses. The European Commission requested a review of the toxicity of fumonisins and the established levels, leading to revisions for poultry and horses based on new evidence. The risk of adverse health effects was considered a concern for poultry, but low for horses and other solipeds.
Article
Food Science & Technology
Dieter Schrenk, Margherita Bignami, Laurent Bodin, James Kevin Chipman, Jesus del Mazo, Bettina Grasl-Kraupp, Christer Hogstrand, Jean-Charles Leblanc, Elsa Nielsen, Evangelia Ntzani, Annette Petersen, Salomon Sand, Tanja Schwerdtle, Christiane Vleminckx, Heather Wallace, Sven Daenicke, Carlo Stefano Nebbia, Isabelle P. Oswald, Elena Rovesti, Hans Steinkellner, Laurentius (Ron) Hoogenboom
Summary: In 2011, EFSA adopted a Scientific Opinion on the risks of T-2 and HT-2 toxins in food and feed for animal health. The study concluded that rumen detoxification of T-2 may not always be complete in ruminants, leading to potential adverse effects. However, data on the effects of T-2 on adult ruminants were limited, and further research is needed.
Article
Food Science & Technology
Dieter Schrenk, Margherita Bignami, Laurent Bodin, James Kevin Chipman, Jesus del Mazo, Bettina Grasl-Kraupp, Laurentius (Ron) Hoogenboom, Jean-Charles Leblanc, Carlo Stefano Nebbia, Elsa Nielsen, Evangelia Ntzani, Annette Petersen, Salomon Sand, Tanja Schwerdtle, Christiane Vleminckx, Heather Wallace, Martin Rose, Bruce Cottrill, Anne Katrine Lundebye, Manfred Metzler, Anna Christodoulidou, Christer Hogstrand
Summary: Following a request from the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM) assessed a decontamination process for fish oils and vegetable oils and fats using activated carbon. The evaluation found that the data provided was insufficient to determine the effectiveness of the decontamination process in reducing pollutant concentrations. Additionally, the process may deplete beneficial constituents. Therefore, the current decontamination process does not comply with the relevant acceptability criteria.
Article
Chemistry, Applied
Sylvia Notenboom, Ans Punt, Rudolf Hoogenveen, Marco J. Zeilmaker, Ron L. A. P. Hoogenboom, Bas G. H. Bokkers
Summary: The calibration of a kinetic model for the transfer of PCDD/Fs and dl-PCBs from feed to the hen's body and eggs has been extended to individual congeners, allowing for a more accurate assessment of the transfer characteristics. The congener-specific approach showed that the fraction transferred to egg yolk fat varied among different congeners, with higher transfer rates for certain PCDD/Fs and dl-PCBs. Comparison with the total TEQ method demonstrated that the latter may overestimate the transfer, particularly for mixtures containing high levels of hexa-, hepta-, and octa-PCDD/Fs.
FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT
(2023)
Article
Toxicology
Jochem Louisse, Styliani Fragki, Deborah Rijkers, Aafke Janssen, Bas van Dijk, Liz Leenders, Martijn Staats, Bas Bokkers, Marco Zeilmaker, Aldert Piersma, Mirjam Luijten, Ron Hoogenboom, Ad Peijnenburg
Summary: The aim of this study was to assess the hepatotoxicity differences of a series of PFASs using human HepaRG liver cells. The results showed that different PFASs had different effects on cellular triglyceride accumulation and gene expression. In vitro relative potency factors (RPFs) were obtained for multiple PFASs, indicating their hepatotoxic potency. The HepaRG model can be used as a screening tool for hazard and risk assessment of PFASs.
ARCHIVES OF TOXICOLOGY
(2023)
Article
Public, Environmental & Occupational Health
Maria Uhl, Greet Schoeters, Eva Govarts, Wieneke Bil, Tony Fletcher, Line Smastuen Haug, Ron Hoogenboom, Claudia Gundacker, Xenia Trier, Mariana F. Fernandez, Argelia Castano Calvo, Marta Esteban Lopez, Dries Coertjens, Tiina Santonen, Lubica Palkovicova Murinova, Denisa Richterova, Katleen De Brouwere, Ingrid Hauzenberger, Marike Kolossa-Gehring, Porhallur Ingi Halldorrsson
Summary: The European Joint Programme HBM4EU conducted research on per- and polyfluoroalkyl substances (PFASs) and found that teenagers in Europe are frequently and highly exposed to PFASs. The main sources of exposure are drinking water and certain foods, and specific workplaces also have high levels of PFASs exposure. Therefore, measures need to be taken to prevent further contamination of the European population.
INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH
(2023)
Article
Chemistry, Applied
Felicia Akuamoa, Patrick P. J. Mulder, Toine F. H. Bovee, Ivonne M. C. M. Rietjens, Ron L. A. P. Hoogenboom
Summary: This study analyzed 64 pyrrolizidine alkaloids (PAs) in herbal supplements sold in Ghana for sexual improvement. Out of the 37 samples analyzed, up to 17 different PAs were identified in 19 samples. Although the PA content in the herbal medicinal preparations was generally lower than in honey samples, their presence was mainly attributed to cross-contamination. The observed levels indicate potential health concerns.
FOOD ADDITIVES & CONTAMINANTS PART B-SURVEILLANCE
(2023)
Article
Medicine, Legal
Michael DeVito, Bas Bokkers, Majorie B. M. van Duursen, Karin van Ede, Mark Feeley, Elsa Antunes Fernandes Gaspar, Laurie Haws, Sean Kennedy, Richard E. Peterson, Ron Hoogenboom, Keiko Nohara, Kim Petersen, Cynthia Rider, Martin Rose, Stephen Safe, Dieter Schrenk, Matthew W. Wheeler, Daniele S. Wikoff, Bin Zhao, Martin van den Berg
Summary: In October 2022, the World Health Organization reevaluated the toxic equivalency factors (TEFs) for chlorinated dioxin-like compounds in a panel convened in Lisbon. This effort utilized an updated database, Bayesian dose response modeling, and meta-analysis to derive Best-Estimate TEFs. Applying these new TEFs may result in lower total toxic equivalents for dioxin-like chemicals.
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2024)
Article
Food Science & Technology
Dieter Schrenk, Margherita Bignami, Laurent Bodin, James Kevin Chipman, Jesus del Mazo, Bettina Grasl-Kraupp, Christer Hogstrand, Laurentius (Ron) Hoogenboom, Jean-Charles Leblanc, Elsa Nielsen, Evangelia Ntzani, Salomon Sand, Tanja Schwerdtle, Christiane Vleminckx, Heather Wallace, Jurgen Gropp, Gunther Antonissen, Guido Rychen, Jose Angel Gomez Ruiz, Matteo Lorenzo Innocenti, Elena Rovesti, Annette Petersen
Summary: The European Food Safety Authority (EFSA) updated its scientific opinion on the risks of ochratoxin A (OTA) in animal feed, stating that the risk for adverse health effects in pigs, chickens for fattening, hens, and rabbits is low.