Ochratoxin A toxicity

Cavin, C., Delatour, T., Marin-Kuan, M., Holzhauser, D., Higgins, L, Bezencon, C., Guignard, G., Junod, S., Richoz-Payot, J., Gremaud, E., Hayes, J.D., Nestler, S., Mantle, P. Schilter, B. (2007) Reduction in antioxidant defences may contribute to ochratoxin A toxicity and carcinogenicity. Toxicol. Sci. 96, 30-39. 

Lebmn, S., Golka, K., Schulze, H. Follmann, W. (2006) Glutathione S-transferase polymorphisms and ochratoxin A toxicity in primary human urothelial cells. Toxicology 224, 81-90. 

Ranaldi, G., Mancini, E., Ferruzza, S., Sambuy, Y. Perozzi, G. (2007) Effects of red wine on ochratoxin A toxicity in intestinal Caco-2/TC7 cells. Toxicol. In Vitro 21, 204-210. Rasonyi, T. (1995) Mechanistic Investigations In ochratoxin A induced nephrotoxicity and their relevance for the sex specific renal tumor Induction in rats. Zurich, Switzerland, University of Zurich (Dissertation ETH No. 11343). 

The mycotoxin ochratoxin A (AAA) (7), which is a possible human carcinogen, continues to receive extensive attention due to its presence in a myriad of foods and beverages (1520, 1521) and its well-established toxicity (teratogenicity, mutagenicity, immunotoxicity, genotoxicity, and carcinogenicity) (1522-1524). Major sources of ochratoxin A are grapes, must, and wine (1525-1533), cereals (1534), beer (1535,1536), dried fruit (1537), roasted coffee (1538), and cocoa products and chocolate (1539). 

Ochratoxin A, the most toxic member of this group of mycotoxins, has been found to be a potent nephrotoxin causing kidney damage in many animal species as well as liver necrosis and enteritis [4, 89, 94-96]. This toxin also acts as a immunosuppressor [96-98], and demonstrates teratogenic [99],... 

Fink-Gremmels J, Jahn A, Blom MJ Toxicity and metabolism of ochratoxin A. Nat Toxins 1995 3 214-220. 

Hoehler D, Marquardt RR Influence of vitamins E and C on the toxic effects of ochratoxin A and T-2 toxin in chicks. Poultry Sci 1996 75 1508-1515. 

Creppy EE, Baudrimont I, Belmadani A, Betbeder AM Aspartame as a preventive agent of chronic toxic effects of ochratoxin A in experimental animals. J Toxicol Toxin Rev 1996 15 207-221. 

Another important and widespread fungal toxin is ochratoxin, which is also found in cereals and, to a lesser extent, in coffee and cocoa beans. The toxin Ochratoxin A is the most commonly found and is produced by the Aspergillus t5rpe of fungus. Exposure occurs in many countries in Europe and affects farm animals as well as humans. The major toxic effect in both humans and animals is kidney damage and cancer of the kidney. The available epidemiological evidence indicates that the disease called Balkan nephropathy is associated with consumption of food contaminated with ochratoxin, and the toxin has been detected in the blood of people living... 

Mycotoxins The mycotoxins are secondary products of fungal metabolism. Numerous mycotoxins have been identified as toxicants in humans and/or animal models with several organ systems, including the kidney, being targets for these fungal products. Perhaps the two mycotoxins that have received the most attention as nephrotoxicants are citrinin and ochratoxin A. These two mycotoxins have received particular interest due to their possible role in endemic Balkan nephropathy. 

Sansing, G. A., Lillehoj, E. B., and Detroy, R. W. 1976. Synergistic toxic effect of citrinin, ochratoxin A and penicillic acid in mice. Toxicon 14, 213-220. 

Ochratoxin A 57 is a highly toxic metabolite isolated from Aspergillus ochraceus Wilh The structure assigned to it on the basis of spectral data, was confirmed by an anambiguous synthesis, which is shown below >. 

Ochratoxin A is the most potent toxin isolated from the mould Aspergillus ochraceus. LD50, oral, rat 20 mg/kg. Acute effects mainly on kidneys, also toxic to neural, reproductive and immune systems and carcinogenic. 

The ochratoxins are a small family of toxic fungal metabolites originally isolated from Aspergillus ochraceus Wilhelm (ref.82). They have subsequently been reported from other Aspergillus species including A. melleus (ref.83,84) and several species of Penicillium (ref. 85-89). Ochratoxins are Icnown to be nephrotoxic and hepatotoxic whilst ochratoxin A is a teratogen (ref.90). Because... 

Ochratoxin A was first evaluated by the Committee at its thirty-seventh meeting (Annex 1, reference 94). The key adverse effects noted involved toxicity to the kidney. The Committee established a provisional tolerable weekly intake (PTWI) of 112 ng/kg body weight (bw), on the basis of deterioration of renal function in pigs, for which the lowest-observed-effect level (LOEL) was 8 pg/kg bw per day, and application of a safety factor of 500. At that time, the Committee recommended that further studies be conducted to elucidate the role of ochratoxin A in causing nephropathy in pigs, the mode of action of ochratoxin A as a kidney carcinogen in rodents and the possible role of ochratoxin A in human disease. 

For this evaluation, the Committee considered new toxicological studies that had become available since the last evaluation these included further studies on developmental toxicity, neurotoxicity, immunotoxicity, nephrotoxicity and geno-toxicity and studies on the mode of action of ochratoxin A in the kidney. The Committee also considered the opinion on ochratoxin A in human food published by the European Food Safety Authority (EFSA) in 2006 (European Food Safety Authority, 2006). New data on analytical methods, sampling protocols and the effects of processing were also considered, together with methods of prevention and control and levels and patterns of food contamination. A new dietary exposure assessment was conducted, and the impact of different MLs for cereals was considered. 

The absorption, distribution, metabolism and excretion of ochratoxin A have been summarized previously by the Committee as follows (Annex 1, reference 153). Ochratoxin A is efficiently absorbed from the gastrointestinal tract, mainly in the small intestine. Information from a number of species shows that it is distributed via the blood, mainly to the kidneys, with lower concentrations being found in liver, muscle and fat. Transfer to milk has been demonstrated in rats, rabbits and humans, but little is transferred to the milk of ruminants, owing to hydrolysis of ochratoxin A into phenylalanine and ochratoxin alpha by the rumenal microflora. The major metabolite of ochratoxin A in all species examined is ochratoxin alpha, formed by hydrolysis of the peptide bond. Ochratoxin alpha and minor hydroxylated metabolites that have been identified are all reported to be less toxic than ochratoxin A itself. Ochratoxin A is excreted in urine and faeces, and the relative contribution of each of these routes in different species is influenced by the extent of the... 

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