Ochratoxin a: Its Cancer Risk and Potential for Exposure

Abstract

Ochratoxin A (OA) is a naturally occurring mycotoxin known to contaminate a variety of foods and beverages. The cancer risk posed by OA was reviewed as relevant to human exposure, regulatory activities, and risk management efforts occurring worldwide, particularly in Europe. OA moves through the food chain and has been found in the tissues and organs of animals, including human blood and breast milk. Results from the National Toxicology Program's rodent bioassays show significantly increased incidence of mammary gland tumors in female rats and kidney tumors in male and female rats given OA orally. Liver tumors in female mice fed OA in the diet have also been observed. In humans, OA exposure has been most often associated with the kidney disease Balkan endemic nephropathy (BEN), symptoms of which include tumors of the kidney and urinary tract. No epidemiological studies have yet adequately evaluated the cancer risk of OA in human populations. Studies have shown OA to be genotoxic as well as immunotoxic, although its mode of action is not fully understood. Organizations and agencies in many countries are currently promulgating standards for OA in foods and beverages. Increased efforts in farm management and food safety are being made to mitigate the risks to public health posed by OA. The U.S. Food and Drug Administration (FDA) is currently evaluating data on OA levels in domestic and imported commodities but has not established official regulations or guidelines for OA in the U.S. food supply.

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).…”

“…The potential involvement of environmental toxins, including mycotoxins, phytotoxins, heavy metals, viruses, and trace element deficiencies, has been widely explored (9)(10)(11), with ochratoxin A being a primary focus of EN research in recent years (12,13). Our investigations into this subject were prompted by the striking clinical and histopathologic similarities between EN and aristolochic acid nephropathy (AAN) (14,15).…”

Ochratoxin A is not detectable in renal and testicular tumours

“…Because of its small molecular weight, OTA is readily filtered by the glomerular membrane and accumulates in kidneys. 3 OTA was detected in human milk 3 and can freely cross the blood placental barrier and was thus associated with DNA adducts in fetal kidneys and testicular tissues. 4 OTA is nephrotoxic, 5 teratogenic, 6 immunosuppressive 7 and carcinogenic 8 in many animal species, including rodents, poultry, canine, fish and swine.…”

“…8 Human studies have linked endemic Balkan nephropathy (EBN) to areas with high OTA food contamination. 3 Furthermore, the consumption of OTA-contaminated pork and coffee has been correlated to testicular cancer incidence in 20 countries. 10 Therefore, we propose a theoretical causal role for OTA in inducing urothelial, renal and testicular cancers.…”

“…1 In most countries, the main sources for OTA human food contamination are cereal grains followed by grape products and wine 2 and to a lesser extent coffee, beans, cocoa, beer, nuts, coriander, black pepper, chili powder and ginger. 3 Animal studies have shown that OTA is mostly absorbed by the small intestine. In the blood, it mainly binds to albumin.…”