Aflatoxins genotoxicity

Genotoxicity test of proflavine, aflatoxin B benzo(a)pyrene and N- 172... 

The exceptional reactivity of aflatoxin B1 exo-8,9-epoxide raises the question of its potential detoxification by EHs. Despite the short half-life, the epoxide does react with DNA (toxification) and glutathione 5-transferases (detoxification), but a role for EH appeared dubious [207], Rat liver or recombinant rat EH has since been shown to provide a modest enhancement of up to 22% in the hydrolysis rate of aflatoxin B1 exo-S,9-epoxide, and to decrease somewhat the genotoxicity of aflatoxin B1 when the ratio of EH to cytochrome P450 is high (ca. 50-fold). Purified human EH provided no such enhancement in hydrolysis, nor did it have a clear effect on genotoxicity. Thus, little evidence exists to support a role for EH in the detoxification of aflatoxin B1 [208],... 

Aflatoxin B, is regarded as hepatocarcinogen and genotoxic (2,9). Exhaustive reviews on toxicity, metabolism, and epidemiological studies are provided by IARC and more recently by several authors (2,4). 

For a food contact material with no relevant genotoxicity or carcinogenicity data with an estimated daily intake (EDI) of < 1.5 pg/p/d, FDA would not normally recommend testing. If the food contact material contained SAs, such as the bisfuran polycyclic substructure of aflatoxin Bj (CASRN 1162-65-8), FDA may recommend additional specific tests due to the potential concern for public safety. 

As discussed, aflatoxins are genotoxic and carcinogenic, and for substances of this type, there is no threshold below which no harmful effect is observed. Subsequently, no tolerable daily intake has been set by the JECFA or any other international or national authority. Limits for foods are set as low as reasonably achievable. The current legislation in the European Union includes a maximum level of 2 pg/kg for aflatoxin B, and 4 pg/kg aflatoxin B1 B2, Gi, and G2 for dried fruits and products processed thereof, intended for direct human consumption or as an ingredient in foodstuffs. 

Earombi, E. O. Adepoju, B. F. Ola-Davies, O. E. Emerole, G. O., Chemoprevention of aflatoxin B1-induced genotoxicity and hepatic oxidative damage in rats by kolaviron, a natural biflavonoid of Garcinia kola seeds, Eur. J. Cancer Prev., 2005, 14, 207-214. 

The concept of metabolic activation developed with AAF was then apphed to PAHs, aflatoxins, nitrosamines, nitrosoureas, hydrazines, urethane, and vinyl chloride. Several metabolic activation schemes are presented in Figure 6.2. In each case a highly reactive electrophilic carbocation is formed. We now know that the concept of metabolic activation applies to many genotoxic carcinogens and helps to explain... 

Genotoxic Diethylnitrosamine Dimethylnitrosamine Aflatoxin Bi Safrole Acetylaminofluorene... 

Mycotoxins are defined as mould derived secondary metabolites, Ochratoxin A and aflatoxin B being the most widely studied. Ochratoxin A (OTA), produced by Aspergillus ochraeus and Penicillium verrucosum, can be found as a contaminant in grain, beer, coffee and meat. OTA is nephrotoxic, carcinogenic and genotoxic [235]. 

Gradelet, S. et al. Modulation of aflatoxin B1 carcinogenicity, genotoxicity and metabolism in rat liver by dietary carotenoids evidence for a protective effect of CYPl A inducers. Cancer Lett., 114,221,1997. 

Guyoimet, D. et al.. Mechanisms of protection against aflatoxin Bi genotoxicity in rats treated by organosulfur compounds from garlic. Carcinogenesis, 23, 1335,2002. 

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