Ochratoxin A: An overview on toxicity and carcinogenicity in animals and humans

Abstract

Ochratoxin A (OTA) is a ubiquitous mycotoxin produced by fungi of improperly stored food products. OTA is nephrotoxic and is suspected of being the main etiological agent responsible for human Balkan endemic nephropathy (BEN) and associated urinary tract tumours. Striking similarities between OTA-induced porcine nephropathy in pigs and BEN in humans are observed. International Agency for Research on Cancer (IARC) has classified OTA as a possible human carcinogen (group 2B). Currently, the mode of carcinogenic action by OTA is unknown. OTA is genotoxic following oxidative metabolism. This activity is thought to play a central role in OTA-mediated carcinogenesis and may be divided into direct (covalent DNA adduction) and indirect (oxidative DNA damage) mechanisms of action. Evidence for a direct mode of genotoxicity has been derived from the sensitive 32P-postlabelling assay. OTA facilitates guanine-specific DNA adducts in vitro and in rat and pig kidney orally dosed, one adduct comigrates with a synthetic carbon (C)-bonded C8-dG OTA adduct standard. In this paper, our current understanding of OTA toxicity and carcinogenicity are reviewed. The available evidence suggests that OTA is a genotoxic carcinogen by induction of oxidative DNA lesions coupled with direct DNA adducts via quinone formation. This mechanism of action should be used to establish acceptable intake levels of OTA from human food sources.

Aristolochic acid and the etiology of endemic (Balkan) nephropathy

“…Considerable attention has been devoted to the hypothesis that a mycotoxin, ochratoxin A (OTA), is the environmental toxin responsible for EN (12,13,42). However, solid epidemiologic evidence supporting an association between OTA exposure and the prevalence of EN or upper urothelial cancer is lacking (43).…”

Validation of a UHPLC-FLD analytical method for the simultaneous quantification of aflatoxin B1 and ochratoxin a in rat plasma, liver and kidney

“…Moreover, OTA is nephrotoxic, hepatotoxic, teratogenic and immunotoxic, and recent studies have related it to neurodegenerative diseases such as Parkinson and Alzheimer [8,9]. Due to the aforementioned, a Tolerable Weekly Intake (TWI) of 120 ng/kg of body weight has been established for OTA [10] but, as of yet there is no threshold for AFB1; therefore, ALARA (as low as reasonably achievable) principle limit must be applied as it is not possible to identify an intake without risk [11].…”

Ochratoxin A in Ruminants–A Review on Its Degradation by Gut Microbes and Effects on Animals

“…Several reviews on different aspects of OTA have been published including overviews on general aspects [12,13,14,15,16], on OTA as a storage mycotoxin [17], on OTA and its mode of action [18,19,20], on carcinogenic potential of OTA [21], on general risk assessment of OTA [22] or on decontamination [23,24]. …”