Plenary lecture in international congress of Mycotoxins (Chiba, 1999). Risk of multi-exposure to natural toxins

After the findings of Uraguchi group that several Penicillium spp. isolated from Yellowed Rice produced hepatocarcinogenic, neurotoxic and nephrotoxic mycotoxins such as cyclochlorotin/luteoskyrin, citreoviridin and citrinin respectively, a relationship between the fungi and their toxic metabolites gave rise a great attention with a special reference to human diseases (Saito et al., 1971). Thereafter, aflatoxins (AFBs, a potent hepatocarcinogen), ochratoxin A (OTA, a nephrotoxin), zearalenone (ZEN, a phytoestrogen) and others were identified from Asp. flavus, Pen. ochraceus, and Fusarium spp., respectively. The isolation of cytotoxic trichothecene, nivelanol (NIV), from F. nivale Fn 2b (Tatsuno, 1968) (reviced to F. kyushuience) (Ueno et al., 1997a) as a causal agent for scabby grain intoxication promoted the research on its natural occurrence and significance for health hazards in humans and animals. Satratoxins, the macrocyclic trichothecenes from air-born fungi such as Stachybotyys atra. are associated with bioaerosols-originated diseases (Ueno and Sugiura,1999c). Beside these foodand air-born mycotoxins, several species of blue-green algae such as Microcystis aeruginosa produce hepatotoxic phycotoxins, microcystins (MCs). These phycotoxins contaminated in environmental and drinking waters were presumed as a risk for primary liver cancer (PLC) (Yu, 1989, 1995). It means that the interaction among food-and air-born mycotoxins and water-derived phycotoxins is a toxicologically important problem to be solved. In order to minimize the risk from these natural toxins, the most countries as well as the international organizations are proposing a maximum acceptable level for each contaminants, particularly on the carcinogenic contaminants such as AFs and OTA, based on risk assessment composed from the following four steps, 1) hazard identification, 2) exposure assessment, 3) dose-response assessment, and 4) risk characterization. However, the risk assessment is carried out mostly for an individual chemical, and no