Hazard characterization of Alternaria toxins to identify data gaps and improve risk assessment for human health.

Solveig Krapf, Igor Snapkow, Jérôme Henri, Julie Sanders, Kyriaki Machera, Laurent Gaté, Ludovic Le Hegarat, Matjaž Novak, Nicola M Smith, Gunnar Sundstøl Eriksen, Sonja Hager, Valérie Fessard, Yvonne Kohl, Maria João Silva, Hubert Dirven, Jessica Dietrich, Doris Marko, Henriqueta Louro, Francesco Crudo, Eszter Borsos, Estelle Dubreil, Elisabeth Varga, Eliana Spilioti, Dieynaba Ndiaye, Christiane Kruse Fæste, Bojana Žegura, Birgit Mertens, Anne-Cathrin Behr, Anne Straumfors, Anita Solhaug, Anastasia Spyropoulou, Adela López de Cerain, Ariane Vettorazzi

Journal: Archives of toxicology 2024;98(2):425-469

PMID: 38147116

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Abstract

Fungi 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.

Address: Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge (INSA) and Centre for Toxicogenomics and Human Health (ToxOmics), NOVA Medical School, Universidade Nova de Lisboa, Av. Padre Cruz, 1649-016, Lisbon, Portugal.; MITOX Research Group, Department of Pharmaceutical Sciences, Faculty of Pharmacy and Nutrition, UNAV-University of Navarra, Pamplona, Spain.; Laboratory of Toxicological Control of Pesticides, Scientific Directorate of Pesticides' Control and Phytopharmacy, Benaki Phytopathological Institute, 145 61, Attica, Greece.; Norwegian Veterinary Institute, PO Box 64, 1431, Ås, Norway.; National Institute of Occupational Health, Gydas Vei 8, 0363, Oslo, Norway.; Department Food Safety, BfR, German Federal Institute for Risk Assessment, Max-Dohrnstraße 8-10, 10589, Berlin, Germany.; Department of Chemical and Physical Health Risks, Sciensano, Brussels, Belgium.; Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna Pot 111, 1000, Ljubljana, Slovenia.; INRS, Institut National de Recherche et de Sécurité pour la Prévention des accidents du travail et des maladies professionnelles, Rue du Morvan, CS 60027, 54519, Vandœuvre Lès Nancy Cedex, France.; Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Vienna, Austria.; Food Hygiene and Technology, University of Veterinary Medicine, Vienna, Veterinärplatz 1, 1210, Vienna, Austria.; Toxicology of Contaminants Unit, Fougères Laboratory, French Agency for Food, Environmental and Occupational Health and Safety, 10 B rue Claude Bourgelat, 35306, Fougères, France.; Department of Chemical Toxicology, Norwegian Institute of Public Health, Lovisenberggate 8, 0456, Oslo, Norway.; Fraunhofer Institute for Biomedical Engineering IBMT, Joseph-Von-Fraunhofer-Weg 1, 66280, Sulzbach, Germany.; Department Safety in the Food Chain, BfR, German Federal Institute for Risk Assessment, Max-Dohrn-Straße 8-10, 10589, Berlin, Germany.; Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Vienna, Austria. [email protected].

DOI: 10.1007/s00204-023-03636-8

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MeSH Terms: Humans, Perylene, Alternaria, Mycotoxins, Mutagens, Lactones, Risk Assessment, Food Contamination