Ochratoxin A: the unknown about a very well-known mycotoxin

Abstract – Ochratoxin A has been regulated in Europe since 2006, with the first official risk assessment dating back to 1994. There have been many efforts over the years in the agro-food system to control, monitor, and mitigate its occurrence in food commodities. However, the recent scientific evaluation of EFSA shed light on several still-open issues, such as OTA’s still-to-be-clarified potential genotoxicity and the possible overall dietary exposure to OTA in the European population due to unregulated food commodities. Although the analytical methods for routine analysis are well-established, data from the monitoring plans used for risk assessment are often incomplete or inaccurate because of inappropriate sensitivity settings. This review is a critical discussion of the scientific efforts needed to close the knowledge gaps and to decrease the uncertainty in risk assessment.    Intro – what OTA is in a nutshell Ochratoxin A (OTA) is a naturally occurring foodborne mycotoxin found in a wide variety of agricultural commodities worldwide, such as grains, seeds and beans, dried fruits, spices, and roots (Streit et al. 2012; Marin et al. 2013). From a chemical point of view, OTA is formed by a phenylalanine moiety linked via an amide bond to a chlorinated dihydroisocoumaric acid. It is produced by several species of the genus Aspergillus, such as A. ochraceus, A. carbonarius and A. niger, and Penicillium. While P. verrucosum is responsible for OTA production in starch-rich foods such as grains and cereal derivatives, P. nordicum has been associated with OTA accumulation in protein-rich food, like fermented meats and cheeses (Bogs et al. 2006; Lund and Frisvad 2003). Due to its stability under moderate heating, OTA can persist along the food production chain. However, losses ranging up to 90% have been observed at temperatures above 180°C, mainly described during coffee bean roasting (Taniwaki et al. 2019). Due to the possible fungal growth on the surface of protein-based food during ripening, OTA has been found in preserved meat and seasoned cheeses (Battilani et al. 2007). Animal food products may also contribute to OTA ingestion via indirect transmission from animals exposed to naturally contaminated feed (carry-over effect) (Gareis and Wolff 2000). Several toxic effects associated with OTA have been reported over the years, including the inhibition/activation of enzymes in protein synthesis and apoptosis, immunosuppression, reduction of immune response in organs, depression of antibody responses, alteration in immune cell activities, and modulation of cytokine production (for more details, see Pfohl-Leszkowicz and Manderville 2007 and references therein). The International Agency for Research on Cancer has included OTA in its Group 2 carcinogens, due to its kidney carcinogenicity (IARC-WHO 1993). The Commission of the European Communities established in Regulation (EC) 1881/2006 maximum admissible levels of OTA for human consumption in many foodstuffs, among them cereals, coffee, grapes, grapefruit, dried vine fruits, wine, spices, and liquorice. From a toxicokinetic point of view, OTA is rapidly absorbed and distributed but slowly eliminated and excreted after ingestion, leading to potential accumulation in the body, which is due mainly to binding to plasma proteins and a low rate of metabolism. Plasma half-lives range from several days in rodents and pigs to several wee

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