Frantisek Malir

Producers and important dietary sources of ochratoxin A and citrinin.

Ochratoxin A (OTA) is a very important mycotoxin, and its research is focused right now on the new findings of OTA, like being a complete carcinogen, information about OTA producers and new exposure sources of OTA. Citrinin (CIT) is another important mycotoxin, too, and its research turns towards nephrotoxicity. Both additive and synergistic effects have been described in combination with OTA. OTA is produced in foodstuffs by Aspergillus Section Circumdati (Aspergillus ochraceus, A. westerdijkiae, A. steynii) and Aspergillus Section Nigri (Aspergillus carbonarius, A. foetidus, A. lacticoffeatus, A. niger, A. sclerotioniger, A. tubingensis), mostly in subtropical and tropical areas. OTA is produced in foodstuffs by Penicillium verrucosum and P. nordicum, notably in temperate and colder zones. CIT is produced in foodstuffs by Monascus species (Monascus purpureus, M. ruber) and Penicillium species (Penicillium citrinum, P. expansum, P. radicicola, P. verrucosum). OTA was frequently found in foodstuffs of both plant origin (e.g., cereal products, coffee, vegetable, liquorice, raisins, wine) and animal origin (e.g., pork/poultry). CIT was also found in foodstuffs of vegetable origin (e.g., cereals, pomaceous fruits, black olive, roasted nuts, spices), food supplements based on rice fermented with red microfungi Monascus purpureus and in foodstuffs of animal origin (e.g., cheese).

Ochratoxin A: 50 Years of Research

Since ochratoxin A (OTA) was discovered, it has been ubiquitous as a natural contaminant of moldy food and feed. The multiple toxic effects of OTA are a real threat for human beings and animal health. For example, OTA can cause porcine nephropathy but can also damage poultries. Humans exposed to OTA can develop (notably by inhalation in the development of acute renal failure within 24 h) a range of chronic disorders such as upper urothelial carcinoma. OTA plays the main role in the pathogenesis of some renal diseases including Balkan endemic nephropathy, kidney tumors occurring in certain endemic regions of the Balkan Peninsula, and chronic interstitial nephropathy occurring in Northern African countries and likely in other parts of the world. OTA leads to DNA adduct formation, which is known for its genotoxicity and carcinogenicity. The present article discusses how renal carcinogenicity and nephrotoxicity cause both oxidative stress and direct genotoxicity. Careful analyses of the data show that OTA carcinogenic effects are due to combined direct and indirect mechanisms (e.g., genotoxicity, oxidative stress, epigenetic factors). Altogether this provides strong evidence that OTA carcinogenicity can also occur in humans.

Mycotoxins as human carcinogens—the IARC Monographs classification

Humans are constantly exposed to mycotoxins (e.g. aflatoxins, ochratoxins), mainly via food intake of plant and animal origin. The health risks stemming from mycotoxins may result from their toxicity, in particular their carcinogenicity. In order to prevent these risks, the International Agency for Research on Cancer (IARC) in Lyon (France)—through its IARC Monographs programme—has performed the carcinogenic hazard assessment of some mycotoxins in humans, on the basis of epidemiological data, studies of cancer in experimental animals and mechanistic studies. The present article summarizes the carcinogenic hazard assessments of those mycotoxins, especially aflatoxins (aflatoxin B1, B2, G1, G2 and M1), fumonisins (fumonisin B1 and B2) and ochratoxin A (OTA). New information regarding the genotoxicity of OTA (formation of OTA-DNA adducts), the role of OTA in oxidative stress and the identification of epigenetic factors involved in OTA carcinogenesis–should they indeed provide strong evidence that OTA carcinogenicity is mediated by a mechanism that also operates in humans–could lead to the reclassification of OTA.

Ochratoxin A: Developmental and Reproductive Toxicity—An Overview

Ochratoxin A (OTA) is nephrotoxic, hepatotoxic, reprotoxic, embryotoxic, teratogenic, neurotoxic, immunotoxic, and carcinogenic for laboratory and farm animals. Male and female reproductive health has deteriorated in many countries during the last few decades. A number of toxins in environment are suspected to affect reproductive system in male and female. OTA is one of them. OTA has been found to be teratogenic in several animal models including rat, mouse, hamster, quail, and chick, with reduced birth weight and craniofacial abnormalities being the most common signs. The presence of OTA also results in congenital defects in the fetus. Neither the potential of OTA to cause malformations in human nor its teratogenic mode of action is known. Exposure to OTA leads to increased embryo lethality manifested as resorptions or dead fetuses. The mechanism of OTA transfer across human placenta (e.g., which transporters are involved in the transfer mechanism) is not fully understood. Some of the toxic effects of OTA are potentiated by other mycotoxins or other contaminants. Therefore, OTA exposure of pregnant women should be minimized. OTA has been shown to be an endocrine disruptor and a reproductive toxicant, with abilities of altering sperm quality. Other studies have shown that OTA is a testicular toxin in animals. Thus, OTA is a biologically plausible cause of testicular cancer in man.

Toxicity of the mycotoxin ochratoxin A in the light of recent data

Abstract Ochratoxin A (OTA) is a ubiquitous, naturally occurring chlorophenolic mycotoxin produced in contaminated food and feed by fungi of genera Penicillium and Aspergillus. OTA is a common contaminant of various foodstuffs of both plant and animal origin. OTA represents significant risk to human and animal health. OTA has been shown to be nephrotoxic, hepatotoxic, teratogenic, immunotoxic, neurotoxic, genotoxic and carcinogenic (possible human carcinogen-group 2B), being characterized by species and sex differences in sensitivity. In some aspects OTA remains as a controversial topic. Its metabolism, genotoxicity and mechanism of action for renal carcinogenicity have been discussed.

Ochratoxin A exposure biomarkers in the Czech Republic and comparison with foreign countries.

Among ochratoxins, ochratoxin A (OTA) occupies a dominant place and represents significant risk for human and animal health which also implies economic losses around the world. OTA is nephrotoxic, hepatotoxic, teratogenic and immunotoxic mycotoxin. OTA exposure may lead to formation of DNA adducts resulting to genotoxicity and carcinogenicity (human carcinogen of 2B group). Now it seems that OTA could be “a complete carcinogen” which obliges to monitor its presence in biological materials, especially using the suitable biomarkers. In this article, OTA findings in urine, blood, serum, plasma and human kidneys (target dose) in the Czech Republic and comparison with foreign countries are presented.

Monitoring of mycotoxin biomarkers in the Czech Republic.

AFM1 was determined in 72 (72%) samples of human urine, range 19-6064 pg/g creatinine, mean 367 pg/g creatinine, median 158 pg/g creatinine and 90% percentile 755 pg/g creatinine in 1997. AFM1 was determined in 46 (43.8%) samples of human urine, range 21-19219 pg/g creatinine, mean 414 pg/g creatinine, median 96 pg/g creatinine and 90% percentile 415 pg/g creatinine in 1998. OTA was determined in 2077 (94.2%) samples of human serum, range 0.1–13.7 μg/L, mean 0.28 μg/L, median 0.2 μg/L and 90% percentile 0.5 μg/L in 1994–2002. OTA was determined in 12 (40%) samples of human kidneys, range 0.1–0.2 μg/kg, mean 0.07 μg/kg, and median 0.05 μg/kg in 2001.

Transfer of ochratoxin A into tea and coffee beverages.

Ochratoxin A (OTA) is nephrotoxic, hepatotoxic, immunotoxic, neurotoxic, reprotoxic, teratogenic, and carcinogenic (group 2B), being characterized by species and sex differences in sensitivity. Despite the fact that OTA is in some aspects a controversial topic, OTA is the most powerful renal carcinogen. The aim of this study was to make a small survey concerning OTA content in black tea, fruit tea, and ground roasted coffee, and to assess OTA transfer into beverages. OTA content was measured using a validated and accredited HPLC-FLD method with a limit of quantification (LOQ) of 0.35 ng/g. The OTA amount ranged from LOQ up to 250 ng/g in black tea and up to 104 ng/g in fruit tea. Black tea and fruit tea, naturally contaminated, were used to prepare tea infusions. The transfer from black tea to the infusion was 34.8% ± 1.3% and from fruit tea 4.1% ± 0.2%. Ground roasted coffee naturally contaminated at 0.92 ng/g was used to prepare seven kinds of coffee beverages. Depending on the type of process used, OTA transfer into coffee ranged from 22.3% to 66.1%. OTA intakes from fruit and black tea or coffee represent a non-negligible human source.

Ochratoxin A levels in blood serum of Czech women in the first trimester of pregnancy and its correspondence with dietary intake of the mycotoxin contaminant

Abstract The mycotoxin ochratoxin A (OTA) can elicit a wide range of toxic properties including embryotoxicity and teratogenicity. OTA crosses the placenta at early gestation rather than in late gestation, maternal OTA exposure may represent a risk for the developing fetus. The study focuses on the assessment of OTA intake of pregnant women (aged 19–40 years) in the first trimester of pregnancy by means OTA levels in 100 blood serum samples by high-performance liquid chromotography with fluorescence detection (HPLC-FD) method and comparison with dietary OTA exposure in pregnant women. Of all, 96% tested serum samples were positive with values ranging from 0.1 to 0.35 µg/l with a mean value of 0.15 µg/l.

Determination of Ochratoxin A in Food by High Performance Liquid Chromatography

Ochratoxin A (OTA) is an important mycotoxin that is produced by Aspergillus and Penicillium species. Ochratoxin A is a common contaminant of various foods including cereals, spices, coffee, cacao, beer, wine, raisins, pulses, meat, meat products, or edible offal. Due to a wide range of its toxic effects in humans and animals, ochratoxin A needs to be monitored. With regard to this necessity, a sensitive HPLC-FD method for purposes of the quantification of trace amounts of ochratoxin A in foods of plant and animal origin was developed, validated and applied for analysis. Food samples were cleaned using commercial immunoaffinity columns and analyzed by means of a high performance liquid chromatography method with fluorescence detection. Limit of quantification of the method ranged between 0.01–0.30 µg/kg depending on the sample matrix. Recoveries were 80–88% in the concentration range of 0.01–0.30 µg/kg, depending upon sample type. The quality of laboratory results was confirmed by successful participation in international inter-laboratory proficiency testing. This laboratory was accredited accordance to CSN ISO/EN 17025. The developed method was applied to the determination of ochratoxin A in samples from 61 types of foodstuffs of plant and animal origin, that were collected in 4 sampling terms at 12 regions of the Czech Republic in years 2011–2012. In total, 732 food samples were gathered and analyzed.