Aflatoxins toxicity/carcinogenicity

Assessment of whether a chemical has the potential to cause adverse effects in humans arises usually from direct observation of an effect in animals or humans, such as the acute poisoning episodes that have occurred when potatoes contain high levels of glycoalkaloids. Epidemiological studies have also been used to infer a possible relationship between intake of a particular type of food, or constituent of that food, and the potential to cause an adverse effect. Such observations led to the characterisation of the aflatoxins as human carcinogens. However, natural toxic substances that occur in plant foods have often been identified through observations in animals, particularly farm animals. It was observations of adverse effects in farm animals that led to the further characterisation of the phytoestrogens and the mycotoxins. In other instances, the concern arises from the chemical similarity to other known toxins. 

Aflatoxin Bi (AFB) is a mold metabolite which has been observed to be acutely toxic and carcinogenic to a wide variety of animals (5,6) and has been implicated in human primary hepatic carcinoma (7, 8). Diets deficient in protein have been reported to increase the susceptibility of mammals to acute AFB toxicity and the induction of cancer (2, 9, 10, 11, 12, 13). Increased dietary proteins have increased the carcinogenic activity of AFB fed to rats (1 4) and trout (15.). Supportive of this latter finding has been the reported direct relationship between dietary protein content and AFB-DNA adduct formation in vivo in rats (16, 17). 

No. The FDA went too far. Aflatoxins can indeed cause liver toxicity in animals and are also carcinogenic. But they produce these adverse effects only at levels far above the FDA set limit. We should ensure some safety margin to protect humans, but 20 ppb is unnecessarily low and the policy that there is no safe level is not supported by scientific studies. Indeed, it s not even certain that aflatoxins represent a cancer risk to humans because animal testing is not known to be a reliable predictor of human risk. Moreover, the carcinogenic potency of aflatoxins varies greatly even among the several animal species in which they have been tested. Human evidence that aflatoxins cause cancer is unsubstantiated. There is no sound scientific basis for the FDA s position. 

The importance of chiral factors in disposition and toxicity has been fully recognized only relatively recently, although important examples have been known for some time. For instance the S(—) enantiomer of thalidomide is known to have greater embryotoxicity than the R(+) enantiomer (see chap. 7). Another example in which a particular isomer of a metabolite is responsible for a carcinogenic effect is the exo-oxide of aflatoxin Bi, discussed later in this chapter (Fig 5.14). 

Aflatoxins B are fungal metabolites and are produced by Aspergillus flavus. There are several related products all contain a phloroglucinol segment in their structure and all are extremely toxic and carcinogenic, eg, aflatoxin B (56) (201). 

Aflatoxins are products of species of the genus Aspergillus, particularly A flavus, a common fungus found as a contaminant of grain, maize, peanuts, and so on. First implicated in poultry diseases such as Turkey-X disease, they were subsequently shown to cause cancer in experimental animals and, from epidemiological studies, in humans. Aflatoxin Bl, the most toxic of the aflatoxins, must be activated enzymatically to exert its carcinogenic effect. 

Bi and Gi are the most highly toxic and are animal carcinogens. Bi is teratogenic in rodents. In countries where food contains aflatoxins, there is an increased incidence of liver cancer. Listed as known human carcinogens.3... 

Hayes (ZZ) observed that in protein-deficient animals, aflatoxin B was more acutely toxic and not as carcinogenic. 

The majority of toxicants in foods are contaminants, (e.g., microbial toxins, pesticide residues, leachable chemicals from packaging materials, food coatings, traces of heavy metals). However, the major issue in food safety is the contamination of food by mycotoxins in items such as milk and milk products, meat and meat products, and peanuts (groundnuts). Aflatoxin is highly toxic and lethal, and its carcinogenic potential is well established, even at doses as low as 0.05. ig. Mycotoxins also infect food products like rice, pulses, tapioca, and betelnuts. (Table 10-2). 

Since the discovery of the Turkey X disease in 1960, aflatoxins have been established as mutagenic, teratogenic and hepatocarcinogenic in experimental animals. AFB] is the most toxic of this group of toxins and the order of toxicity is Bi>Gi>B2>G2. Aflatoxin M] is 10-fold less toxic than Bj, but its presence in milk is of concern in human health [66-68]. AFBj is also one of the most carcinogenic natural compounds known therefore, extensive research has been done on its synthesis, toxicity and biological effects [53, 69-72]. 

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