Mycotoxins. 1

2 Mycotoxins are secondary metabolites produced by microfungi that are capable of causing disease and death in humans and other animals. The majority of mycotoxicoses result from eating contaminated foods. Skin contact with mold-infested substrates and inhalation of spore-borne toxins are also important sources of exposure. Except for supportive therapy (e.g., diet, hydration), there are almost no treatments for mycotoxin exposure.

3 CLASSIFICATION: Clinicians often arrange them by the organ they affect. Thus, mycotoxins can be classified as hepatotoxins, nephrotoxins, neurotoxins, immunotoxins, and so forth. Cell biologists put them into generic groups such as teratogens, mutagens, carcinogens, and allergens. Organic chemists have attempted to classify them by their chemical structures (e.g., lactones, coumarins); biochemists according to their biosynthetic origins (polyketides, amino acid-derived, etc.); physicians by the illnesses they cause (e.g., St. Anthony's fire, stachybotryotoxicosis), and mycologists by the fungi that produce them (e.g., Aspergillus toxins, Penicillium toxins).

4 The four major aflatoxins are called B 1, B 2, G 1, and G 2 based on their fluorescence under UV light (blue or green) The toxicity of the six most potent aflatoxins decreases in the following order: B1 > M1 > G1 > B2 > M2 # G2.3 When viewed under ultraviolet (UV) light, six of the toxins fluoresce as noted: BJ and B2—blue G1—green G2—green-blue M1—blue-violet M2—violet MAJOR MYCOTOXINS AFLATOXINS

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6 Aflatoxins are produced by by many strains of Aspergillus flavus and Aspergillus parasiticus; in particular. Aspergillus flavus is a common contaminant in agriculture.

7 With respect to production in foods, aflatoxin has been demonstrated on fresh beef, ham, and bacon inoculated with toxigenic cultures and stored at 15°, 20°, and 30 0 C. They have been found in a wide variety of foods, including milk, beer, cocoa, raisins, soybean meal, and so on.

8 Codex Alimentarius Commission has recommended the following maximum levels of mycotoxins in specific foods: 15 ug/kg of aflatoxins in peanuts for further processing; 0.05 jug/kg of aflatoxin M1 in milk; 50 ug/kg of patulin in apple juice and apple juice ingredients in other beverages; and 5 µ g/kg of ochratoxin A in cereals and cereal products.

9 Relative Toxicity and Mode of Action Most species of susceptible animals die within 3 days after administration of toxins and show gross liver damage, which, upon postmortem examination, reveals the aflatoxins to be hepatocarcinogens. Circumstantial evidence suggests that aflatoxins are carcinogenic to humans. Aflatoxin B 1 is the most potent natural carcinogen known and is usually the major aflatoxin produced by toxigenic strains.

10 ALTERNARIA TOXINS Several species of Alternaria (including A. citri, A. alternata, A. solani, and A. Tenuissima) produce toxic substances. They are in apples, tomatoes, blueberries, grains, and other foods. The toxins produced include alternariol, alternariol monomethyl ether, altenuene, tenuazonic acid, and altertoxin-I.

11 CITRININ The citrinin mycotoxin is produced by Penicillium citrinum, P.vindication, and other fungi. Under long-wave UV light, it fluoresces lemon yellow. It is a known carcinogen.

12 OCHRATOXINS The ochratoxins consist of a group of at least seven structurally related secondary metabolites of which ochratoxin A (OA) is the best known and the most toxic. OA is produced by a large number of storage fungi, including A. ochraceus,A. alliaceus,A. ostianus, A. mellus, and other species of aspergilli. Among penicillia that produce OA are P. viridicatum, P. cyclopium, P variable, and others.

13 OA mycotoxin has been found in corn, dried beans, cocoa beans, soybeans, oats, barley, citrus fruits. OA fluoresces greenish, while OB emits blue fluorescence. It induces abnormal mitosis in monkey kidney cells.

14 PATULIN Patulin (clavicin, expansin) is produced by a large number of penicillia, including P. claviforme, P expansum, R patulum; by some aspergilli (A. clavatus, A. terreus, and others). This mycotoxin has been found in moldy bread, sausage, fruits (including bananas, pears, pineapples, grapes, and peaches), apple juice, cider, and other products.

15 The LD50 for patulin in rats by the subcutaneous route is 15 to 25 mg/kg, and it induces subcutaneous sarcomas in some animals. Patulin causes chromosomal aberrations in animal and plant cells and is a carcinogen.

16 PENICILLIC ACID This mycotoxin has biological properties similar to patulin. It is produced by a large number of fungi, including many penicillia (P.puberulum, for example) as well as members of the A. ochraceus group. It has been found in corn, beans, and other field crops. It is a proved carcinogen.

17 STERIGMATOCYSTIN These mycotoxins are structurally and biologically related to the aflatoxins, and like the latter, they cause hepatocarcinogenic activity in animals. At least eight derivatives are known. Among the organisms that produce them are Aspergillus versicolor, A. nidulans, and A. rugulosus.

18 Under UV light, the toxin fluoresces dark brick-red. Although not often found in natural products, they have been found in wheat, oats, Dutch cheese, and coffee beans. While related to the aflatoxins, they are not as potent. They act by inhibiting DNA synthesis.

19 FUMONISINS The fumonisins are produced by Fusarium spp. on corn and other grains. The species demonstrated to produce fumonisins include E anthophilum, E dlamini, F. napiforme, F. nygami, F. moniforme, and F.proliferation Certain disease of humans and animals are associated with the consumption of grains and grain products that contain high levels of these molds.

20 There are at least seven fumonisins, four Bs and at least three As: FB1, FB2, FB3, FB4, FA1, FA2, and FA3. The major ones are FB1-FB3, and the others are considered to be minor and less well characterized. High levels of fumonisins are found in grain-based foods. In experimental animals, the liver is the primary target of FB1.