Special Issue "Ochratoxins"

Guest Editor
Prof. Dr. Richard A. Manderville
Department of Chemistry and Toxicology, University of Guelph, Guelph, Ontario, N1G 2W1 Canada
Website: http://www.chemistry.uoguelph.ca/manderville/webpage.htm
E-Mail:
Interests: DNA damage by phenolic toxins including ochratoxin A; Modified DNA bases as fluorescent probes

Guest Editor
Prof. Dr. Annie Pfohl-Leszkowicz
National Agronomical High School of Toulouse (ENSAT), Unit of Toxicology & Food safety, 1 avenue de l’Agrobiopôle, BP 107, 31326, Auzeville-Tolosane, France
E-Mail:
Interests: mycotoxin; ochratoxin; fumonisin; zearalenone; biomarker; risk evaluation; environmental toxicology; polycyclic aromatic compounds; genotoxicity; DNA adduct; balkan endemic nephropathy; kidney cancer; biotransformation

Dear Colleagues,

In the seminal paper published in Nature, 1965, van Der Merwe, Steyn, Fourie, Scott and Theron, reported the isolation of a new toxic metabolite, called ochratoxin A (now abbreviated OTA), from Aspergillus ochraceus. Structural analysis of the mycotoxin pointed to the presence of a chlorophenolic moiety containing a dihydroisocoumarin system amide-linked to L-phenylalanine with toxicity in ducklings of the same order as that of aflatoxin B1 from Aspergillus flavus. Subsequent experimental carcinogenicity studies in male rats and mice carried out in the 1980s demonstrated OTA to be a potent kidney carcinogen and highlighted the real possibility that OTA could be a human carcinogen. OTA causes kidney damage in farm animals and a number of studies also suggested a correlation between OTA exposure and a fatal human kidney disease called Balkan endemic nephropathy, in which patients exhibit a high incidence of urinary tract tumours. OTA is now regarded as the most toxic member of the ochratoxins, which have attracted considerable attention since they are one of the most abundant food-contaminating mycotoxins in the world and are classified as potentially carcinogenic to humans (Group 2B). Ongoing interdisciplinary research on the ochratoxins have been concerned with detection in feed and human foodstuff, occurrence and estimation of dietary intake, establishment of limits for human consumption based on risk assessment and understanding mechanisms of toxicity and carcinogenicity for the development of detoxification processes. We hope that this special issue of Toxins entitled “Ochratoxins” will provide the readership with a better understanding of the key issues being addressed at the present time.

Prof. Dr. Richard A. Manderville
Prof. Dr. Annie Pfohl-Leszkowicz
Guest Editors

Submission

All manuscripts should be submitted to toxins@mdpi.org with a copy to the Guest Editor. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed Open Access monthly journal published by MDPI.

• ochratoxins
• mycotoxin
• carcinogen
• Balkan endemic nephropathy
• DNA damage
• genotoxic
• intake
• biotransformation
• risk assessment

Type of Paper: Article
Title: Differential Cell Sensitivity between OTA and LPS upon Releasing TNF-α
Authors: L. Al-Anati ¹, E. Essid ¹, K. Beuerlein ², K. Schuh ¹ and Ernst Petzinger ¹
Affiliations: ¹ Institute of Pharmacology and Toxicology, College of Veterinary Medicine, Justus Liebig University Giessen. Frankfurter Street 107. D-35392 Giessen, Germany; E-Mail: ernst.petzinger@vetmed.uni-giessen.de (E.P.)
² Rudolf-Buchheim-Institute of Pharmacology, College of Medicine, Justus Liebig University Giessen. Frankfurter Street 107, D-35392 Giessen, Germany
Abstract: The release of tumor necrosis factor α (TNF-α) by ochratoxin A (OTA) was studied in various macrophage and non-macrophage cell lines and compared with E. coli lipopolysaccharide (LPS) as a standard TNF-α release agent. Cells were exposed either to 0, 2.5 12.5 µmol/L OTA or to 0.1 µg/ml LPS for up to 24 hrs. OTA at 2.5 µmol/L and 0.1 µg/ml LPS are not toxic to the tested cells. TNF-a was detected in the incubated cell medium of rat Kupffer cells, peritoneal rat macrophages, and the mouse monocyte macrophage cell line J774A.1. TNF-a concentrations were 1000 pg/ml, 1560pg/ml, and 650 pg/ml respectively for 2.5 µmol/L OTA exposure and 3000 pg/ml, 2600 pg/ml, and 2115 pg/ml respectively for LPS exposure. Rat liver sinusoidal endothelial cells, rat hepatocytes, human HepG2 cells, and mouse L929 cells lacked any cytokine response to OTA but showed significant release of TNF-a from LPS exposure, except for HepG2 cells. Our data indicate that only macrophages and macrophagocytic cells are more sensitive to OTA and considered the sources for TNF-a release upon OTA exposure. In contrast, LPS induced the release of TNF-a from a wide variety of macrophage and non-macrophage cell types.
Keywords: Ochratoxin A; lipopolysaccharide; tumor necrosis factor α; Kupffer cells; macrophages; rat liver sinusoidal endothelial cells; HepG2 cells; rat hepatocytes
Abbreviations: Ochratoxin A (OTA); tumor necrosis factor (TNF); Lipopolysaccharide (LPS)

Type of paper: Review
Title: Ochratoxins in Feeds, A Risk for the Animal and the Human Health: Control Strategies
Authors: M. Denli ¹, S. Salado ², M.E. Guynot and J.F. Perez ³
Affiliations: ¹ Dicle University, Agricultural Faculty, Department of Animal Science, 21280, Diyarbakir, Turkey
² Adiveter, Agro-Reus, Reus, 43205 Tarragona, Spain
³ Grup de Recerca en Nutrició, Maneig i Benestar Animal, Departament de Ciència Animal i dels Aliments, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain
Abstract: Ochratoxin A (OTA) has been shown to be a potent nephrotoxic, hepatotoxic, and teratogenic compound. In farm animals, the intake of feed contaminated with OTA impacts the animal health and productivity, and may result in the presence of OTA in the animal products. Strategies for the control of OTA in food products require an early identification and elimination of contaminated commodities from the food chain. However, current protocols of analyses may fail on the identification of contaminated products, especially in feeds for animal feeding. The present paper overviews the impact of OTA in the human and animal health, with a special emphasis on the potential risks of OTA residues in animal products, and control strategies applied in the feed industry.
Keywords: Ochratoxins; toxicity; human; animals; control strategies

Type of paper: Article
Title: Ochratoxin A on Surface of Sausages of Different Areas of North Italy: Occurence, Prevention and Elimination
Authors: Serena Milesi ¹, Silvia Pirani ¹, Luca Chiesa ¹, Carlo Cantoni ¹ and Giuseppe Comi ^2,*
Affiliations: ¹ Dipartimento di Scienze e Tecnologie Veterinarie per la Sicurezza degli Alimenti, Facoltà di Medicina Veterinaria, Università degli Studi di Milano, via Celoria 10, 20133 Milano, Italy
² Dipartimento di Scienze degli Alimenti, Facoltà di Agraria, Università degli Studi di Udine, via Sondrio 2, 33100 Udine, Italy; E-Mail: giuseppe.comi@uniud.it (G.C.)
Abstract: The moulds on sausage surface are necessary to lead to successful production or consumer appeal. However in some cases an uncontrolled growth of particular moulds can lead to presence of of highly toxic secondary metabolites: mycotoxins. The aim of the paper was to investigate the presence of Ochratoxin A (OTA) and ochratoxin producing moulds on the surface of traditional sausages of some areas of North Italy, which included Central Alps area (Valtellina valley), Prealpes Area (Brianza), Appennines Mountains Area (Oltrepò Pavese), Central Padana Valley (upper Po river) and North East (Veneto/Friuli). Additional aim was to prevent the growth of ochratoxigenic moulds or to eliminate them by the use of brushing and washing the sausages before selling or by ozonated air during drying and ripening. Penicillium nordicum, P.chrysogenum, P.verrucosum and Aspergillus ochraceus were the main ochratoxigenic moulds, isolated on the casings. A.ochraceus was the most frequently identified species. About 67% of the total samples presented an OTA concentration more than 1 µg/Kg. OTA was found only on the surfaces of sausages and not in the meat. An OTA concentration less than 50 µg/Kg was found on the casing contaminated by Penicillium OTA producing strains, whereas more than 50 µg/Kg on the casing contaminated by A. ochraceus. OTA was reduced less than the LOD by brushing and washing the sausages before selling and no OTA producing strains were found on surfaces of sausages treated during the drying/ripening by ozonated air. From that data it seems that the presence of OTA on surface of sausages (in casings) is not indicative of any food health risk for humans consuming sausages, considering that OTA was not identified inside the dry meat.
Keywords: Fermented sausages; casings; moulds; Ochratoxin A, safety.

Type of Paper: Article
Title: Ochratoxin A and β2-Microglobulin in BEN Patients and Controls
Authors: Pavlina Yordanova ¹, Karmaus Wilfried ², Svetla Tsolova ¹ and Plamen Dimitrov ¹
Affiliations: ¹ National Center of Public Health Protection, 1431 Sofia, Bulgaria; E-Mails: p.jordanova@ncphp.government.bg (P.Y.); sv.tzolova@ncphp.government.bg (S.T.); p.dimitrov@ncphp.government.bg (P.D.)
² Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, South Carolina, USA; E-Mail: karmaus@mailbox.sc.edu (K.W.)
Abstract: Ochratoxin A (OTA) is an ubiquitous, potently nephrotoxic and carcinogenic mycotoxin, naturally occurring in different types of food. OTA is considered a human health risk. The occurrence of OTA in populations has been measured in many countries. Ochratoxin A gained importance for human health after suspicion that it may be involved in the pathogenesis of Balkan endemic nephropathy. BEN occurs only in some areas of Bosnia and Herzegovina, Bulgaria, Croatia, Rumania, and Serbia and Montenegro. The aim of our study was to test OTA-BEN association in BEN-patients (n=19), offspring of BEN patients (n=38), and controls (n=22), and to determine whether β2-microglobulin urine excretion is related to OTA serum levels. Geometric mean levels of OTA were 1.19, 0.76, and 0.72 ng/mL in BEN patients, offspring of BEN patients, and offspring of controls, respectively. Ochratoxin A serum levels were significantly higher in BEN patients (p=0.02). However, serum collection in different seasons of the year affected the OTA concentrations. Within the adult offspring of BEN and non-BEN patients, OTA was statistically significantly associated with a higher β2-microglobulin urine excretion. Our results are suggested of the hypothesis that OTA may be related to BEN.
Keywords: BEN; Ochratoxin A; β2-microglobulin

Title: Occurrence of Black Aspergilli and Ochratoxin A on Grapes in Italy
Authors: G.L. Lucchetta, I. Bazzo, G.L. Dal Cortivo, L. Stringher, D. Bellotto, E. Angelini and M. Borgo
Affiliation: CRA-VIT Centro di Ricerca per la Viticoltura, Conegliano (TV ), Italy; E-Mail: elisa.angelini@entecra.it
Abstract: Ochratoxin A (OTA) in wine is linked to contamination with Aspergillus spp. During 2001-2006, grape samples collected in Italy were surveyed for the presence of OTA and OTA-producer species. A. niger was the prevalent species in the samples, followed by A. carbonarius, mostly found in samples from southern Italy. The years and the environment had a determining influence on the development of black Aspergillus populations. Determination of OTA by ELISA showed it to be present in about 40% of the samples. In particular, samples from southern Italy showed the highest occurrence (75%) and also the highest concentration of OTA, sometimes higher than 2 mg/ml. The values decreased progressively towards the north of Italy.

Type of Paper: Review
Title: Ochratoxins, Food Contaminants: Impact on Human Health
Authors: L. Reddy ¹ and Kanti D. Bhoola ²
Affiliations: ¹ Department of Biotechnology and Food Technology, Durban University of Technology, Durban, South Africa
² Lung Institute of Western Australia, University of Western Australia, Perth WA, Australia; E-Mail: profbhoola@iinet.net.au
Abstract: Ochratoxins are secondary metabolites of Aspergillus and Penicillium, that are hazardous to human health through contamination of dietary foods. Ochratoxin A (OTA) remains the single most potent member of this group of mycotoxins. OTA has a long half life in humans and is thus easily detected in serum. Dietary intake studies have confirmed link between EN in humans to their daily household intake of OTA (Abouzied et al., 2002). OTA has been reported to contribute to human endemic nephrotoxicity (EN) and carcinogenicity in humans and animals. OTA produces renal tumours, DNA adducts and chromosomal aberrations in the kidneys (Walker and Larsen, 2005). Although OTA has not been found to be mutagenic, it may be embryotoxic, teratogenic, and immunotoxic only at doses higher than those causing nephrotoxicity. The incidence of EN has been mostly reported in northeast Europe since the early nineties (Fuchs and Peraica, 2005). Recent studies however have warned that OTA and mycotoxins, such as aristolochic acid (AA), show very similar renal pathology (Peraica et al., 2008). There is thus the need for thorough co-occurrence studies on mycotoxin incidence.

Type of Paper: Review
Title: Molecularly Imprinted Polymers for Ochratoxin Extraction and Analysis
Authors: Edward Lai ¹ and Jorn Chi Chung Yu ²
Affiliation: ¹ Department of Chemistry, Ottawa-Carleton Chemistry Institute, Carleton University, Ottawa, ON K1S 5B6, Canada; E-Mail: edward_lai@carleton.ca
² College of Criminal Justice, Sam Houston State University, Box 2525, 1003 Bowers Blvd., Huntsville, TX 77341, USA; E-Mail: jornyu@shsu.edu
Abstract: Molecularly imprinted polymers (MIPs) have been considered as polymeric materials that mimic functionalities of antibodies. MIPs have been utilized for a wide variety of applications in chromatography, immunoassay, solid phase extraction, and sensor devices, where the MIPs function as recognition elements. In this review, recent advances of MIPs for the extraction and analysis of ochratoxins are discussed. Selection of functional monomers, optimization of extraction procedures, and limitations of MIP are compared from different reports. Strategies on the preparation of MIP and schemes of analytical methods are also reviewed in order to suggest the next step to make use of MIPs in the field of ochratoxin research.
Keywords: molecularly imprinted polymer; ochratoxin; solid phase extraction; analysis

Type of Paper: Review
Title: Ochratoxin A Occurrence in Foods and Biological Fluids in Portugal: A Review
Authors: S. C. Duarte, A. Pena and Celeste M. Lino
Affiliation: Group of Health Surveillance, CEF, Faculty of Pharmacy, University of Coimbra, Health Sciences Campus, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; E-Mail: cmlino@ci.uc.pt (C.M.L.)
Abstract: A review on the occurrence of ochratoxin A (OTA) in Portuguese foodstuffs and biological fluids is given. The assessment of OTA exposure in Portugal through evaluation of their occurrence in food and biological fluids (blood and urine), both in the general population and in some at-risk groups of consumers is presented. OTA has been more extensively studied in different types of bread as well as in organic and non-organic cereals, such as rice, wheat, maize, oats, barley, rye and spelt. The incidence of OTA in wines from different regions of Portuguese, such as Douro Demarcated Region (Port Wine and Vinho Verde), has also deserved special attention. Occasionally, OTA was also evaluated in infant formulae and in meat products. As a main output of this review and considering the results both in foods and biological fluids, we could conclude that the presence of OTA does not constitute a public health problem.

Type of Paper: Review
Title: Incidence and daily intake of Ochratoxin A in Spain
Authors: J. Blesa, C. Soler, J.M. Soriano, J.Mañes
Affiliation: Department of Preventive Medicine and Public Health, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain; E-Mail: Jose.Soriano@uv.es
Abstract: The contamination of OTA is elevated in several foods (cereals, wine, beers, coffee among others); this fact is relationated with possible hazardous daily intake. This value is legally fixed in the tolerable daily intake (TDI) with values of 5 ng/kg b.w./day according to the Scientific Committee on Food of the European Commission and 16 ng/kg b.w./day the FAO/WHO Committee of Experts on Food Additives. The aim of this review is to know the incidence in several foods commercilalized in Spain and daily intake in Spanish people. It is the first review about incidence and daily intake of OTA in this country.

Title: Mechanism of Ochratoxin A Carcinogenicity
Authors: Maricel Marin-Kuan*, Thierry Delatour, Cavin Christophe; Veronika Erhlich, Benoît Schilter
Affiliation: Nestlé Research Center, PO Box 44, Vers-chez-les-Blanc, CH-1000 Lausanne 26, Switzerland; E-Mail: maricel.marin-kuan@ rdls.nestle.com (M. M.-K.)
Abstract: The mechanism of ochratoxin A (OTA) carcinogenicity is still unclear. In the present review, the in vitro and in vivo evidence compatible with a role for oxidative stress will be collected and critically assessed. Several potential oxido-reduction mechanisms have been identified in the past. More recently, the possibility of a reduction of cellular antioxidant defense has been raised as an indirect source of oxidative stress. The actual consequences and toxicological significance of an OTA-mediated stimulation of oxidative stress will be evaluated. Its role together with or as alternative of other potential mechanisms such as DNA-adduct formation will be discussed in the context of the establishment of a safe level of OTA human exposure.

Manuscript ID: Toxins-ochratoxins-01
Type of Paper: Article
Title: Studies on carcinogenic and toxic effects of ochratoxin A in chicks and the protective properties of some feed additives
Author: Stoycho D. Stoev
Affiliation: Department of General and clinical pathology, Faculty of Veterinary Medicine, Trakia University, Students campus, 6000 Stara Zagora, Bulgaria; E-Mail: stoev@uni-sz.bg
Abstract: A protective effect of feed additives: water-extract of artichoke (WEA), sesame seed (SS), Roxazyme-G (RG) and phenylalanine (PHE) against the carcinogenic/toxic effects of ochratoxin A (OTA) in Plymouth Rock chicks was found. The number of OTA-induced neoplasms was less in PHE-treated group and no neoplasms were found in chicks treated with WEA, SS and RG. OTA was found to provoke strong degenerative changes in liver and kidneys, degenerative changes and depletion of cells in lymphoid organs, oedematous and degenerative changes in the brain, muscular haemorrhages and fatty changes in the bone marrow. The target organs for carcinogenic effect of OTA in chicks were found to be kidneys and liver.
Key words: ochratoxin A; protection; feed additives; carcinogenic effect; chicks; pathomorphology

Manuscript ID: Toxins-ochratoxins-02
Type of Paper: Article
Title: Determination of Toxigenic molds and mycotoxins in pigs feed from Serbian farms: potential rapid and selective methods
Authors: Dragan Milicevic ¹, Miomir Nikšic ², Tatjana Baltic ¹, Danijela Vranic ¹ and Srdan Stefanovic ¹
Affiliations: ¹ Institute of Meat Hygiene and Technology, Kacanskog 13, 11000 Belgrad, Serbia; E-Mails: dragan@inmesbgd.com (D. M.); tanja_baltic@yahoo.com (T. B.) daniv@inmesbgd.com (D.V.), ssrdjan@inmesbgd.com (S.S.)
² University of Belgrade, Faculty of Agriculture, Institute of Food Technology and Biochemistry, Nemanjina 6, 11080 Zemun, Serbia; E-Mail: mniksic@agrifaculty.bg.ac.rs (M.N.)
Abstract: In order to assess of risk assessment, the aim of this paper was to provide good and detailed insight into the level of contamination of complete feedmixes intended for fattening swine from mycotoxin-producing fungi and mycotoxins (n=18). Isolation and
quantitative enumeration of fungal propagules were done on solid media using the standard microbiological procedure. These plates were incubated the number of colonies was determined and thent on the basis of characteristic colonies and microscopic analysis was performed to identify genera and species of moulds. Isolates identified as Aspergillus and Penicillium species were subjected to molecular characterization of the presence of genes responsible for the synthesis of OTA (polyketide synthase gene-PKS). Total fungal counts (CFU/g) ranged from 0,5x105 do 4x106. From a total samples analysed, seven samples had fungal counts higher than the limit established by Serbian regulations (3x105). During a mycological analysis of complete feedmixes intended for fattening swine, a total of six genera and 14 species of moulds were identified of which the most frequent one was of the genus Penicillium (94,4%) while the moulds from Fusarium genere isolated in 55,5% and Paecilomyces in 44,4% of the samples from investigated localities. Other fungi from the genera Aspergillus (22%), Mycor (11,1%) and Alternaria (5,5%) were represented in a less amount. Polymerase chain reaction (PCR) is a set of 18 isolates of the DNA belonging to families Penicillium and Aspergillus. The sequences of PCR reaction products in three samples were compared with nucleotide sequences of genes for poliketid synthase (PKS) from Penicillium species and found that the samples possess PKS sequence. The traditional methods for identification of ochratoxin-producing fungi are time-consuming and labor-intensive. Rapid and specific detection of ochratoxin-producing fungi is important for ensuring microbiological quality and safety of feed and food.
Keywords: Toxogenic moulds; Mycotoxins; pig feed; detremination; risk assessment

Type of Paper: Review
Title: Effects of Ochratoxin A on Livestock Production
Author: Gianni Battacone
Affiliation: Dipartimento di scienze zootecniche, università degli studi di sassari, via enrico de nicola, 9, 07100 sassari, Italy; E-Mail: battacon@uniss.it
Abstract: Ochratoxin A (OTA) contamination of animal feed causes large economic losses on livestock production. The intake of feed contaminated by OTA also represents a potential risk for animal health and a food safety issue due to the transfer of the toxin through the human food chain. The aim of this paper is to review the available literature on: 1) the frequency and degree of occurrence of OTA in different feedstuffs; 2) the toxicological effects of OTA intake on the performance of the main livestock species (i.e. poultry, swine, cattle, goats and sheep); and 3) the passage of OTA, or its metabolites, from animal feed into animal products such as milk, meat and eggs.

Type of Paper: Article
Title: Ochratoxin A Contamination of Food in Croatia
Authors: Maja Peraica ¹, Dubravka Flajs ¹, Ana-Marija Domijan ¹, Dario Ivić ² and Bogdan Cvjetković ²
Affilation: ¹Unit of Toxicology, Institute for Medical Research and Occupational Health, Ksaverska c. 2, 10000 Zagreb, Croatia; E-Mail: mperaica@imi.hr (M.P.)
² Department of Phytopathology, Faculty of Agriculture, Svetošimunska 25, 10000 Zagreb, Croatia
Abstract: Ochratoxin A (OTA) is a mycotoxin with nephrotoxic properties produced by Penicillium and Aspergillus moulds in all climatic conditions. Humans and animals are exposed to this genotoxic and carcinogenic compound mostly by ingestion of contaminated food. In Croatia, the research of OTA started because of the mycotoxin theory of Balkan endemic nephropathy (BEN), kidney disease known in a region of our country. OTA was found more frequently or in higher concentration in food from BEN than in control regions. Afterwards, its concentrations were checked in some items intended for human consumption (maize, wheat, beans and wine). In our studies samples were collected from all parts of Croatia, and OTA was found in all analyzed commodities. It was frequently found together with other mycotoxins (fumonizin B₁, fumonizin B₂ and zearalenone). In general, the OTA concentration in food in Croatia is low but the frequency of positive samples shows considerable variations depending on the location of sampling. Although the OTA concentration in food is low, the co-occurrence with other mycotoxins shows that the thorough control is needed.

Manuscript ID: Toxins-ochratoxins-05
Type of Paper: Review
Title: Ochratoxin A: General Discussion and Actual Molecular Status
Authors: André El Khoury ¹ and Ali Atoui ²
Affiliations: ¹ Centre d’analyses et de recherches, Faculté des Sciences, Université Saint-Joseph, Beyrouth, Lebanon
² Lebanese Atomic Energy Commission-CNRS, P.O. Box 11-8281, Riad El Solh, 1107 2260 Beirut, Lebanon; E-Mail: a.atoui@cnrs.edu.lb
Abstract: Ochratoxin A (OTA) is a mycotoxin produced by several species of Aspergillus and Penicillium fungi that structurally consists of a para-chlorophenolic group containing a dihydroisocoumarin moiety that is amidelinked to L-phenylalanine. OTA is detected worldwide in various food and feed sources. Studies showed that this molecule can have several toxicological effects such as nephrotoxic, hepatotoxic, neurotoxic, teratogenic and immunotoxic. Its implication role in the etiology of Balkan endemic nephropathy and its association to urinary tract tumours has been also proved. In this review we will explore the general aspect of OTA: physico-chemical properties, toxicological profile, OTA producing fungi, contaminated food, reglementation and legislation and analytical methods. Due to lack of sufficient informations related to the molecular background this paper will deeply treat the recent advances in molecular biology of OTA biosynthesis based on information and on new data about identification and characterization of ochratoxin biosynthetic genes in both Penicillium and Aspergillus species. This review also will cover the development of the molecular methods for the detection and quantification of OTA producing fungi in various foodstuffs.
Keywords: Ochratoxin A; toxicity; polyketide synthase gene; molecular biology; biosynthesis; detection; quantification