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

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.

First Report on Mycotoxin Contamination of Hops (Humulus lupulus L.)

“…With these new data, they could be included in a monitoring plan, risk assessment by EFSA, or legislation due to a relatively high maximum concentration of TeA (1174 µg/kg), exceeding most of the proposed limits in the Commission recommendations (EC 553/2022) [13] on monitoring the presence of Alternaria toxins in food. The concentrations of the other two Alternaria toxins mentioned in the legislation do not exceed the proposed limits, although they should not be excluded from monitoring due to their toxicities [42]. When comparing the locations of the sampling, the highest average…”

New approach methodologies to enhance human health risk assessment of immunotoxic properties of chemicals — a PARC (Partnership for the Assessment of Risk from Chemicals) project

“…In the PARC project, beside the development of NAMs for immunotoxicity which are not targeting specific substances, other partners have focused on particular data-poor substances such as BPA alternatives and mycotoxins. These PARC priority substances have been extensively reviewed by PARC partners in separate publications ( Kodila, Franko, and Sollner Dolenc, 2023 ; Louro et al, 2024 ).…”

Unraveling Interspecies Differences in the Phase I Hepatic Metabolism of Alternariol and Alternariol Monomethyl Ether: Closing Data Gaps for a Comprehensive Risk Assessment

“…They have been reported to possess cytotoxic, − genotoxic and mutagenic, − immunosuppressive, , and potential endocrine disruptive , properties. This complex pattern of often overlaying effects is comprehensively summarized in a recent review by Louro et al…”

“…They have been reported to possess cytotoxic, 3−5 genotoxic and mutagenic, 6−9 immunosuppressive, 10,11 and potential endocrine disruptive 12,13 properties. This complex pattern of often overlaying effects is comprehensively summarized in a recent review by Louro et al 14 Alternaria species have a wide host range, thriving on grains, fruits, tomatoes, sunflower seeds, olives, etc. Their ubiquity, resilience, and ability to withstand even low temperatures allow them to contaminate foods after harvest and persist during storage or transport, even under refrigeration.…”