Aflatoxin B1

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Aflatoxin B1
(–)-Aflatoxin B1 Structural Formulae V.1.svg
Chemical structure of (–)-Aflatoxin B1
3D Structure of aflatoxin B1
IUPAC name
Other names
NSC 529592
3D model (Jmol)
ECHA InfoCard 100.013.276
Molar mass 312.28 g·mol−1
Main hazards Very Toxic Very Toxic T+
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Aflatoxin B1 is an aflatoxin produced by Aspergillus flavus and A. parasiticus. It is arguably the most potent carcinogen known, and is up to twice as carcinogenic as an equitoxic dose of X-rays. Aflatoxin B1 is a common contaminant in a variety of foods including peanuts, cottonseed meal, corn, and other grains;[1] as well as animal feeds.[2] Aflatoxin B1 is considered the most toxic aflatoxin and it is highly implicated in hepatocellular carcinoma (HCC) in humans.[3] In animals, aflatoxin B1 has also been shown to be mutagenic,[4] teratogenic,[5] and to cause immunosuppression.[6] Several sampling and analytical methods including thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), mass spectroscopy, and enzyme-linked immunosorbent assay (ELISA), among others, have been used to test for aflatoxin B1 contamination in foods.[7] According to the Food and Agriculture Organization (FAO), the worldwide maximum tolerated levels of aflatoxin B1 was reported to be in the range of 1–20 µg/kg in food, and 5–50 µg/kg in dietary cattle feed in 2003.[8]

Sources of exposure[edit]

Aflatoxin B1 is mostly found in contaminated food and humans are exposed to aflatoxin B1 almost entirely through their diet.[9] Occupational exposure to aflatoxin B1 has also been reported in swine[10] and poultry production.[11]


Aflatoxin B1 can permeate through the skin. Dermal exposure to this aflatoxin in particular environmental conditions can lead to major health risks.[12] The liver is the most susceptible organ to aflatoxin B1 toxicity. In animal studies, pathological lesions associated with aflatoxin B1 intoxication include reduction in weight of liver,[13] vacuolation of hepatocytes,[14] and hepatic carcinoma.[15] Other liver lesions include enlargement of hepatic cells, fatty infiltration, necrosis, hemorrhage, fibrosis, regeneration of nodules, and bile duct proliferation/hyperplasia.[16]

Biosynthetic pathway[edit]

Aflatoxin B1 is derived from both a dedicated fatty acid synthase (FAS) and a polyketide synthase (PKS), together known as norsolorinic acid synthase. The biosynthesis begins with the synthesis of hexanoate by the FAS, which then becomes the starter unit for the iterative type I PKS.[17][18][19] The PKS adds seven malonyl-CoA extenders to the hexanoate to form the C20 polyketide compound. The PKS folds the polyketide in a particular way to induce cyclization to form the anthraquinone norsolorinic acid. A reductase then catalyzes the reduction of the ketone on the norsolorinic acid side-chain to yield averantin.[17][18][19] Averantin is converted to averufin via a two different enzymes, a hydroxylase and an alcohol dehydrogenase. This will oxygenate and cyclize averantin's side chain to form the ketal in averufin.

From this point on the biosynthetic pathway of aflatoxin B1 becomes much more complicated, with several major skeletal changes. Most of the enzymes have not been characterized and there may be several more intermediates that are still unknown.[17] However, what is known is that averufin is oxidized by a P450-oxidase, AvfA, in a Baeyer-Villiger oxidation. This opens the ether rings and upon rearrangement versiconal acetate is formed. Now an esterase, EstA, catalyzes the hydrolysis of the acetyl, forming the primary alcohol in versiconal.[17][19] The acetal in versicolorin A is formed from the cyclization of the side-chain in versiconal, which is catalyzed by VERB synthase, and then VerB, a desaturase, reduces versicolorin B to form the dihydrobisfuran.[17][19]

There are two more enzymes that catalyze the conversion of versicolorin A to demethylsterigmatocystin: AflN, an oxidase and AflM, a reductase. These enzymes use both molecular oxygen and two NADPH's to dehydrate one of the hydroxyl groups on the anthraquinone and open the quinine with the molecular oxygen.[17][19] Upon forming the aldehyde in the ring opening step, it is oxidized to form the carboxylic acid and subsequently a decarboxylation event occurs to close the ring, forming the six-member ether ring system seen in demethylsterigmatocystin. The next two steps in the biosynthetic pathway is the methylation by S-adenosyl methionine (SAM) of the two hydroxyl groups on the xanthone part of demethysterigmatocystin by two different methyltransferases, OmtB and OmtA.[17][19] This yields O-methylsterigmatocystin. In the final steps there is an oxidative cleavage of the aromatic ring and loss of one carbon in O-methylsterigmatocystin, which is catalyzed by OrdA, an oxidoreductase.[17][19] Then a final recyclization occurs to form aflatoxin B1.


Several aflatoxin B1 toxicity studies have been conducted on various animal species.[20]

Acute toxicity
The oral LD50 range of aflatoxin B1 is estimated to be 0.3-17.9 mg/kg body weight for most animal species.[21] For instance, the oral LD50 of aflatoxin B1 is estimated to be 17.9 mg/kg body weight in female rats and 7.2 mg/kg body weight in male rats. Still in male rats, the intraperitoneal LD50 of aflatoxin B1 is estimated to be 6.0 mg/kg body weight.[22]
Subacute toxicity
Subacute toxicity studies of aflatoxin B1 in animals showed moderate to severe liver damage. In monkeys for instance, subacute toxicity studies showed portal inflammation and fatty change.[23]
Chronic toxicity
Chronic toxicity studies of aflatoxin B1 in chicken showed decreased hepatic microsomal cytochrome P-450 concentration, reduction in feed consumption and decreased weight gain.[24]
Subchronic toxicity
Subchronic toxicity studies of aflatoxin B1 in fish showed fish to present with preneoplastic lesions, concurrently with changes in gill, pancreas, intestine and spleen.[25]
Treatment of human liver cells with aflatoxin B1 at doses that ranged from 3-5 µmol/l resulted in the formation of aflatoxin B1-DNA adducts, 8-hydroxyguanine lesions and DNA damage.[26]
The carcinogenicity of aflatoxin B1, which is characterized by the development of liver cell carcinoma, has been reported in rat studies.[27]
Embryonic death and impaired embryonic development of the bursa of Fabricius in chicken by aflatoxin B1 has been reported.[28]
The teratogenic effects of aflatoxin B1 in rabbits have been reported to include reduced fetal weights, wrist drop, enlarged eye socket, agenesis of caudal vertebrae, micropthalmia, cardiac defects, and lenticular degeneration, among others.[29]
Studies in fish showed aflatoxin B1 to have significant immunosuppressive effects including reduced serum total globulin and reduced bactericidal activities.[30]

Risk Management and Regulations[edit]

Aflatoxin B1 exposure is best managed by measures aimed at preventing contamination of crops in the field, post-harvest handling, and storage, or via measures aimed at detecting and decontaminating contaminated commodities or materials used in animal feed. For instance, biological decontamination involving the use of a single bacterial species, Flavobacterium aurantiacum has been used to remove aflatoxin B1 from peanuts and corn.[31]

Several countries around the world have rules and regulations governing aflatoxin B1 in foods and these include the maximum permitted, or recommended levels of aflatoxin B1 for certain foods.[32]

United States (US)
US food safety regulations have set a maximum permitted level of 20 μg/kg for aflatoxin B1, in combination with the other aflatoxins (B2, G1 and G2) in all foods, with the exception of milk which has a maximum permitted level of 0.5 μg/kg. Higher levels of 100–300 μg/kg are tolerable for some animal feeds.[33][34]
European Union (EU)
The EU has set maximum permitted levels for aflatoxin B1 in nuts, dried fruits, cereals and spices to range from 2-12 μg/kg, while the maximum permitted level for aflatoxin B1 in infant foods is set at 0.1 μg/kg.[35] The maximum permitted levels for aflatoxin B1 in animal feeds set by the EU range from 5-50 μg/kg and these levels are much lower than those set in the US.[36]
Joint United Nations’ Food and Agriculture Organization (FAO)/World Health Organization (WHO) Expert Committee on Food Additives (JECFA)
The FAO/WHO JECFA has set the maximum permitted levels of aflatoxin B1 in combination with the other aflatoxins (B2, G1 and G2) to be 15 μg/kg in raw peanuts and 10 μg/kg in processesd peanut; while the tolerance level of aflatoxin B1 alone is 5 μg/kg for dairy cattle feed.[37][38]


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