Browsing by Author "Behr, Anne-Cathrin"
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- Hazard characterisation of the mycotoxins enniatins and Alternaria toxins to close data gaps and improve risk assessment for human healthPublication . Dietrich, Jessica; Marko, Doris; Behr, Anne-Cathrin; Driven, Hubert; Silva, Maria João; Louro, Henriqueta; PARC 5.1.1.a Project TeamMycotoxins are secondary metabolites of fungi that may contaminate food and feed, e.g., cereals, (dried) fruits and spices. As they are natural substances, there are no manufacturers or suppliers responsible for providing hazard data, in contrast to e.g. industrial chemicals or pesticides. Humans are widely exposed to mycotoxins mainly through diet and, due to climate changes, the human exposure to these toxins will likely increase. Accordingly, regulatory agencies need more hazard data, particularly regarding emerging (non-regulated) toxins to improve risk assessment and consumer protection. Thus, this project was designed in order to fill data gaps with regulatory relevance regarding the main representatives of two groups of emerging mycotoxins - enniatins and Alternaria toxins. Within the project, in vitro assays on genotoxic, carcinogenic, immunotoxic and endocrine effects of enniatins and Alternaria toxins as well as in silico analyses and further studies on adverse outcome pathway will be performed by a total of 16 partners from the European Union and Norway. Standardized OECD test guidelines as well as so-called New Approach Methodologies will be used to generate in vitro data. The results of the study are expected to identify critical toxicological effects of the toxins for subsequent in vivo studies required to establish health based guidance values and thus to perform an appropriate risk assessment in order to provide an efficient health consumer protection.
- Hazard characterization of Alternaria toxins to identify data gaps and improve risk assessment for human healthPublication . Louro, Henriqueta; Vettorazzi, Ariane; López de Cerain, Adela; Spyropoulou, Anastasia; Solhaug, Anita; Straumfors, Anne; Behr, Anne-Cathrin; Mertens, Birgit; Žegura, Bojana; Fæste, Christiane Kruse; Ndiaye, Dieynaba; Spilioti, Eliana; Varga, Elisabeth; Dubreil, Estelle; Borsos, Eszter; Crudo, Francesco; Eriksen, Gunnar Sundstøl; Snapkow, Igor; Henri, Jérôme; Sanders, Julie; Machera, Kyriaki; Gaté, Laurent; Le Hegarat, Ludovic; Novak, Matjaž; Smith, Nicola M.; Krapf, Solveig; Hager, Sonja; Fessard, Valérie; Kohl, Yvonne; Silva, Maria João; Dirven, Hubert; Dietrich, Jessica; Marko, DorisFungi of the genus Alternaria are ubiquitous plant pathogens and saprophytes which are able to grow under varying temperature and moisture conditions as well as on a large range of substrates. A spectrum of structurally diverse secondary metabolites with toxic potential has been identified, but occurrence and relative proportion of the different metabolites in complex mixtures depend on strain, substrate, and growth conditions. This review compiles the available knowledge on hazard identification and characterization of Alternaria toxins. Alternariol (AOH), its monomethylether AME and the perylene quinones altertoxin I (ATX-I), ATX-II, ATX-III, alterperylenol (ALP), and stemphyltoxin III (STTX-III) showed in vitro genotoxic and mutagenic properties. Of all identified Alternaria toxins, the epoxide-bearing analogs ATX-II, ATX-III, and STTX-III show the highest cytotoxic, genotoxic, and mutagenic potential in vitro. Under hormone-sensitive conditions, AOH and AME act as moderate xenoestrogens, but in silico modeling predicts further Alternaria toxins as potential estrogenic factors. Recent studies indicate also an immunosuppressive role of AOH and ATX-II; however, no data are available for the majority of Alternaria toxins. Overall, hazard characterization of Alternaria toxins focused, so far, primarily on the commercially available dibenzo-α-pyrones AOH and AME and tenuazonic acid (TeA). Limited data sets are available for altersetin (ALS), altenuene (ALT), and tentoxin (TEN). The occurrence and toxicological relevance of perylene quinone-based Alternaria toxins still remain to be fully elucidated. We identified data gaps on hazard identification and characterization crucial to improve risk assessment of Alternaria mycotoxins for consumers and occupationally exposed workers.
- Hazard characterization of the mycotoxins enniatins and beauvericin to identify data gaps and improve risk assessment for human healthPublication . Behr, Anne-Cathrin; Fæste, Christiane Kruse; Azqueta, Amaya; Tavares, Ana M.; Spyropoulou, Anastasia; Solhaug, Anita; Olsen, Ann-Karin; Vettorazzi, Ariane; Mertens, Birgit; Zegura, Bojana; Streel, Camille; Ndiaye, Dieynaba; Spilioti, Eliana; Dubreil, Estelle; Buratti, Franca Maria; Crudo, Francesco; Eriksen, Gunnar Sundstøl; Snapkow, Igor; Teixeira, João Paulo; Rasinger, Josef D.; Sanders, Julie; Machera, Kyriaki; Ivanova, Lada; Gaté, Laurent; Le Hegarat, Ludovic; Novak, Matjaz; Smith, Nicola M.; Tait, Sabrina; Fraga, Sónia; Hager, Sonja; Marko, Doris; Braeuning, Albert; Louro, Henriqueta; Silva, Maria João; Dirven, Hubert; Dietrich, JessicaEnniatins (ENNs) and beauvericin (BEA) are cyclic hexadepsipeptide fungal metabolites which have demonstrated antibiotic, antimycotic, and insecticidal activities. The substantial toxic potentials of these mycotoxins are associated with their ionophoric molecular properties and relatively high lipophilicities. ENNs occur extensively in grain and grain-derived products and are considered a food safety issue by the European Food Safety Authority (EFSA). The tolerable daily intake and maximum levels for ENNs in humans and animals remain unestablished due to key toxicological and toxicokinetic data gaps, preventing full risk assessment. Aiming to find critical data gaps impeding hazard characterization and risk evaluation, this review presents a comprehensive summary of the existing information from in vitro and in vivo studies on toxicokinetic characteristics and cytotoxic, genotoxic, immunotoxic, endocrine, reproductive and developmental effects of the most prevalent ENN analogues (ENN A, A1, B, B1) and BEA. The missing information identified showed that additional studies on ENNs and BEA have to be performed before sufficient data for an in-depth hazard characterisation of these mycotoxins become available.