Review Article

An Overview of Mycotoxins in Human Health with Emphasis on Development and Progression of Liver Cancer

Saurabh Kumar Chhonker, Divya Rawat, Rayees Ahmad Naik and Raj Kumar Koiri*
Department of Zoology, Dr. Harisingh Gour Central University, India

*Corresponding author: Raj Kumar Koiri, Department of Zoology, Dr. Harisingh Gour Central University, India

Published: 06 Feb, 2018
Cite this article as: Chhonker SK, Rawat D, Naik RA, Koiri RK. An Overview of Mycotoxins in Human Health with Emphasis on Development and Progression of Liver Cancer. Clin Oncol. 2018; 3: 1408.


Contamination of food and feed by mycotoxins has become serious problem worldwide. Contamination of human food with mycotoxin at different stages of food chain has also been observed. Aspergillus, Alternaria, Claviceps, Fusarium, Penicillium and Stachybotrys constitute some of the most important genera of mycotoxins. Amongst them, in recent times due to the genotoxic substance aflatoxin B1 being produced by Aspergillus flavus and Aspergillus parasiticus, food contamination by it has been an area of major concern from the point of view of human health as it is a potent hepatocarcinogenic substance. Along with Aspergillus other mycotoxins are nephrotoxic, nephrocarcinogenic and also affect the reproductive system. Case studies from the last two decade suggest that people living and working in damp and moldy area has greater chances of developing asthma, bronchitis, skin diseases and other health disorder.
Keywords: Aflatoxin; Fungi; Hepatocellular carcinoma; Mycotoxin


Mycotoxins are a structurally diverse group of small molecular weight compounds, which are chiefly produced by the secondary metabolism of fungi, or molds, under suitable temperature and humidity conditions. It is produced on different type of food stuff and is directly and indirectly hazardous for both human and animal’s health. Fungi are extremely adaptable organisms and are able to metabolize a large variety of substrates over a wide range of environmental conditions and they produce mycotoxins only under aerobic condition [1]. It has been estimated that 25% of the world’s crops are affected by moulds or fungal growth [2]. Mycotoxins have toxic effects on both human and animals health which is called mycotoxicosis and the level of toxicity of different mycotoxins depends on the quantity of toxins, age of animals, time of exposure and also vary with species to species. Mycotoxins are generally found in arid, humid region and temperate region and have been reported to contaminate human food with its toxic secondary metabolites at various stages in the food chain and their continued exposure has been reported to cause diseases in both human and animal [3]. Prolonged storage of crops in hot and humid conditions has been observed to promote growth of the afltoxin-producing fungi and accumulation of the toxin [4,5]. Some of the most important genera of mycotoxicogenic fungi (Aspergillus, Alternaria, Claviceps, Fusarium, Penicillium and Stachybotrys) have been reported to arise on human food and animal feed components such as corn, sorghum, wheat, barley, peanuts, and other legumes and oil seeds. A wide range of commodities can be contaminated with mycotoxins both at pre- and post-harvest stage [6] (Table 1).

Mycotoxin Exposure and Detection

Exposure to mycotoxins can occur in human and other animals through contamination of cereal grains, other seeds with untraced fungi. There are basically five broad groups of mycotoxins namely aflatoxin, vomitoxin, ochratoxin A, fumonisin and zearalenone. Frequently contamination of aflatoxins has been observed in maize, dry fruits, peanuts etc. In case of ochratoxin a contamination has been reported in wine coffee and cereals, whereas with fumonisin traces have been reported in maize and maize made products. Mycotoxins have exhibited high mutagenic, carcinogenic and teratogenic effect on animals and human after exposure and are thus hazardous. Amongst them notably, aflatoxin is highly dangerous due to its potent carcinogenic and mutagenic property; the hydroxylated metabolite aflatoxin B1 and aflatoxin M1 is excreted into milk from 1 to 6% of dietary intake [7]. To detect mycotoxin contamination several chromatographic methods has been employed notable being HPLC to detect the concentration of mycotoxins in plasma. Another successful approach has been to use DNA adducts to determine exposure to aflatoxin B1 [8] and ochratoxin A [9,10].

Table 1

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Table 1
Human diseases caused by mycotoxins contamination.

Mycotoxins and Human Disease

Mycotoxins are responsible for many type of acute and chronic disease in human and other species. Beardall and Miller have given a very detailed account of human illnesses that have been associated with mycotoxin ingestion [11]. Aflatoxin B1which is toxic metabolite of Aspergillus flavus and Aspergillus parasiticus has exhibited both chronic and acute genotoxic and carcinogenic properties and is the most potent natural carcinogen reported [13]. In dairy cattle, another problem arises from the transformation of AFB1 and AFB2 into hydroxylated metabolites, aflatoxin M1 and M2 (AFM1 and AFM2), which are found in milk and milk products obtained from livestock that have ingested contaminated feed [12]. Aflatoxin B1 is the most potent natural carcinogen known and is usually the major aflatoxin produced by toxigenic strains [13]. Mycotoxins have teratogenic, acute, chronic, mutagenic hemorrhagic, hepatotoxic, nephrotoxic and neurotoxic types of toxicity and in humans they have been reported to damge liver and kidney and if left untreated can progressively lead to death. Their toxicity is mainly due to interruption of protein synthesis and DNA replication, necrosis, lung infection and decreased immunity and can also exhibit mutagenic and teratogenic effects. Long term exposure to mycotoxin has been reported to cause brain damage, induction of cancer in liver and death [14]. With respect to reproductive health, although it has been hypothesized that aflatoxins have adverse effects on birth outcomes but so far there is no critical summary of the literature on the subject [15].

Mycotoxins and Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers world-wide and there is an attaining geographic variation in incidence. More than 80% of all HCC cases has been reported to occur in developing countries, and approximately 55% of all cases from China (especially in the southeast areas such as Guangxi) [16]. Due to very poor prognosis resulting from metastasis and reoccurrence, HCC is the third leading cause of cancer related deaths in the world [17]. After a long four decades of study, including experimental data and epidemiological studies in human populations, aflatoxin B1 (AFB1) has been classified as carcinogenic to humans by the International Agency for Research on Cancer [18]. Historically, several epidemiological studies conducted in Asia and Africa have shown an association between high aflatoxin exposure, estimated by sampling foodstuffs or by dietary questionnaires, and increased incidence of HCC [18]. Although chronic HBV infection is the major risk factor for HCC, other environmental exposures such as drinking alcohol, tobacco smoking and aflatoxins in particular have also been suggested to increase the risk [19]. Numerous studies have demonstrated that a linear correlation exists between serum AFB1 dietary exposure and the risk of HCC development [20]. Aflatoxins are metabolized by hepatic enzymes and in the process generate reactive epoxide species that are able to form a covalent bond with guanine [21] (Figure 1). Another mycotoxin, Ochratoxin A has been reported to be teratogenic in rat, hamster and chick embryo, and is an inhibitor of hepatic mitochondrial transport systems and causes damage to liver and has been reported to be excreted in milk of animals contaminated with it [22,23].

Effect of Mycotoxin on Organ other than Liver

Review of literature suggests that although hepatotoxicity and to some extent renal toxicity has been the focus of researchers globally but it also affects other organs directly like brain and they have been classified under a separate class known as neuromycotoxins and includes tremorgens, trichothecenes, citreoviridin, patulin, fumonisin. Infact study suggests that the primary site of trichothecene action is the brain [24] and the primary clinical symptoms are eye pain, nausea, muscle tremor, vomiting, dyspnea, weakness, etc. Neurophysiological effects of mold exposure have been reported in children as compared with controls [25]. Exposure to aflatoxin differs from species to species and has been reported to decrease reproductive rate, cause embryo death, teratogenicity and tumors. Zearalenone which is a non steroid esterogenic mycotoxin is insoluble in water and is also heat-stable and persists in both animal feeds and is also present in foodstuffs and foods. At lower dose, zearalenone has been reported to effect female estrogen hormone and increase the maturity time of mammary gland whereas at higher doses interferes with conception and is secreted in the milk thus affecting the viability of newborn animals [26,27]. Another mycotoxin, Ochratoxin A, apart from its teratogenic property and liver carcinogenicity has also been reported to cause nephrotoxicity and damage gut and lymphoid tissue particularly at higher doses [22].

Figure 1

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Figure 1
Mechanisms of action of aflatoxin and the development of hepatocellular carcinoma.

Prophylactic Measures to Prevent Mycotoxicity and HCC

Depending on the environmental and substrate conditions, various mycotoxins may occur simultaneously or singly and their contamination always has adverse effects on the health of human and animals [28]. To prevent the adverse effect, first approach is the elimination of mycotoxin exposure especially of hazardous ones like aflatoxin, which is known to cause hepatocellular carcinoma. To prevent and decrease the incidences of liver cancer, vaccination can be promoted to improve immunity. Apart from this, it has also been demonstrated in animal studies and in some human studies that oltipraz is an effective agent in blocking aflatoxin adducts formation and thereby prevents the development and progression of cancer. Mechanism is speculated to be via induction of aflatoxin detoxifying enzymes [21]. Pre-clinical studies and cancer prevention trials that use biomarkers as intermediate endpoints to assess the efficacy of promising chemopreventive agents has shown that several agents can provide some level of protection against aflatoxin-induced liver cancer in experimental systems [29,30]. Since mycotoxins are known to pass through animals and human by contaminated food stuff and dietary product, primary prevention of mycotoxin exposure can be checked by increasing standardization storage, handling of crops and food stuffs both pre and post harvesting stage.

Control of Moulds and Mycotoxins in Animal Feeds

Moulds and mycotoxin contamination in animal food and feed can be easily attained by keeping moisture under control, maintenance of temperature unfavourable to their growth and cleaning of equipment’s. Thus, aeration of grain bins is important to reduce moisture migration and keep the feedstuff dry [27]. Binding agents such as bentonite, alumino silicates, spent canola oil; bleaching clays and alfalfa fiber have been used in feeds containing mycotoxins to prevent intestinal absorption of the toxins [31]. Other substances which have antimycotics properties can be used like cinnamon, cinnamon oil, clove and clove oil [32]. Various physical and chemical strategies have also been developed to help prevent mycotoxin contamination, including physical separation, extraction with sorbents, and adsorption [33]. Some of the common methods that have been employed to analyze mycotoxins are thin layer chromatography, high performance liquid chromatography with UV or fluorescence detection, liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. Ultraviolet light can also be employed to screen aflatoxin contamination and is cheap and cost effective [34].


Economic impact of mycotoxins on both human and animal health is very large in both developing as well as developed countries. Globally all the countries are suffering from huge economic losses due to mycotoxin contamination of food stuffs. Further, it also increases the propensity of hepatitis B and C induced HCC and can also have adverse effect on other human organs. Attempts should be made to find means to lower fumonisins, aflatoxin and mycotoxin contamination as a whole to an acceptable level for a better happier and healthier world.


  1. Ratcliff J. The role of mycotoxins in Food and Feed Safety. Presented at AFMA (Animal Feed Manufacturers Association). 2002;
  2. Mannon J, Johnson E. Fungi down on the farm. New Sci. 1985;105:12-16.
  3. Bennett JW and Klich M. Mycotoxins. Clin Microbiol Rev. 2003;16(3):497- 516.
  4. Strosnider H, Azziz-Baumgartner E, Banziger M, Bhat RV, Breiman R, Brune MN, et al. Work group report: Public health strategies for reducing aflatoxin exposure in developing countries. Environ Health Perspect. 2006;114(12):1898-1903.
  5. Liu Y, Chang CC, Marsh GM and Wu F. Population attributable risk of aflatoxin-related liver cancer: systematic review and meta-analysis. Eur J Cancer. 2012;48(14):2125-36.
  6. Council for Agricultural Science. Mycotoxins: risks in plant, animal and human systems. Council for Agricultural Science and Technology, Ames, Iowa.USA. 2003;
  7. Van Egmond HP. Aflatoxin M1 occurrence, toxicity, regulation. In: van Egmond H.P. eds Mycotoxins in Dairy Products. Elsevier Applied Science Publishers, Barking, Essex, England. 1989;11-55.
  8. Makarananda K, Pengpan U, Sriskulthong M, Yoovathaworn K and Sriwatanakul K. Monitoring of aflatoxin exposure by biomarkers. J Toxicol Sci. 1998;23(2):155-9.
  9. Pfhohl-Leskzkowicz A, Grosse Y, Castegnaro M, Nicolov IG, Chernozemsky IN, Bartsch H, et al. Ochratoxin A-related DNA adducts in urinary tract tumors of Bulgarian subjects. IARC Sci. Publ. 1993;(124):141- 8.
  10. Pfhohl-Leszkowicz A, Grosse Y, Kane A, Creppy EE and Dirheimer G. Differential DNA adduct formation and disappearance in three mouse tissues after treatment with mycotoxin ochratoxin A. Mutat Res. 1993;289(2):265-73.
  11. Beardall JM and Miller JD. Diseases in humans with mycotoxins as possible causes. In: Miller J.D. and Trenholm H.L. eds, Mycotoxins in Grain: Compounds other than Aflotoxin. Egan Press, St Paul Minnesota. 1994;487-539.
  12. Boudra H, Barnouin J, Dragacci S and Morgavi DP. Aflatoxin M1 and ochratoxin a in raw bulk milk from French dairy herds. J Dairy Sci. 2007;90(7):3197-201.
  13. Squire RA. Ranking animal carcinogens: a proposed regulatory approach. Science. 1981;214(4523):877-80.
  14. Smith JE and Moss MO. Mycotoxins: Formation, Analysis and Significance. Chichester, UK: John Wiley & Sons Ltd. 1985;1-148.
  15. Turner P, Collinson A, Cheung Y, Gong Y, Hall A, Prentice A, et al. Aflatoxin exposure in utero causes growth faltering in Gambian infants. Int J Epidemiol 2007;36(5):1119-25.
  16. Xia Q, Huang XY. Xue F, Zhang JJ, Zhai B, Kong DC et al. Genetic polymorphisms of DNA repair genes and DNA repair capacity related to aflatoxin b1 (AFB1)-induced DNA damages. In New Research Directions in DNA Repair. 2013;377-412.
  17. Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.
  18. Aflatoxins. IARC Monograph Evaluation Carcinogenic Risks to Humans. 1993;56:245-395.
  19. McGlynn KA and London WT. Epidemiology and natural history of hepatocellular carcinoma. Best Pract Res Clin Gastroenterol. 2005;19(1):3- 23.
  20. Long XD, Yao JG, Huang YZ, Huang XY, Ban FZ, Yao LM, et al. DNA repair gene XRCC7 polymorphisms (rs#7003908 and rs#10109984) and hepatocellular carcinoma related to AFB1 exposure among Guangxi population, China. Hepatol Res. 2014;41(11):1085-93.
  21. Wild CP and Turner PC. The toxicology of aflatoxin as a basis for public health decisions. Mutagenesis. 2002;17(6):471-81.
  22. Harwig J. Ochratoxin A and related metabolites. Mycotoxins. 1974;345- 367.
  23. Akande KE, Abubakar MM. Adegbola TA and Bogoro SE. Nutritional and health implications of mycotoxins in animal feeds: A review. Pak J Nutr. 2006;5(5):398-403.
  24. Wang J, Fitzpatrick DW and Wilson JR. Effects of the trichothecene mycotoxin T-2 toxin on the neurotransmitters and metabolites in discrete areas of the rat brain. Food Chem Toxicol. 1998;36(11):947–53.
  25. Anyanwu EC, Campbell AW and Vojdani A. Neurophysiological effects of chronic indoor environmental exposure on children. Sci World J. 2003;3:281–90.
  26. Shipchandler MT. Chemistry of zearalenone and some of its derivatives. Heterocycles 1975;3:471-520.
  27. Jones FT, Genter MB, Hagler WM, Hansen JA, Mowrey, BA. Poore MH, et al. Understanding and coping with effects of mycotoxins in livestock feed and forage. North Carolina Cooperative Extension Service. 1994;1-14.
  28. Sohn HB, Seo JA and Lee YW. Co-occurrence of Fusarium mycotoxins in mouldy and healthy corn from Korea. Food Addit Contam. 1999;16(4):153- 158.
  29. Kensler TW, Groopman JD and Roebuck BD. Use of aflatoxin adducts as intermediate endpoints to assess the efficacy of chemopreventive interventions in animals and man. Mutat Res. 1998;402(1-2):165-72
  30. Maurya BK and Trigun SK. Fisetin Modulates Antioxidant Enzymes and Inflammatory Factors to Inhibit Aflatoxin-B1 Induced Hepatocellular Carcinoma in Rats. Oxid Med Cell Longev. 2016;1-9.
  31. Smith TK and Seddon IR. Toxicological synergism between Fusarium mycotoxins in feeds. mIn: Biotechnology in the Feed Industry. (eds, Lyons, T. P. and Jacques, K. A., Nottingham University Press, Loughborough, U. K. 1998;257-69.
  32. Bullerman LB, Lieu FY and Seier SA. Inhibition of growth and aflatoxin production by cinnamon and clove oils, cinnamic aldehyde and eugenol. J Food Sci. 1977;42(4):1107-09.
  33. Sinha KK. Detoxification of mycotoxins and food safety. In: Sinha, K.K., Bhatnagar, D. (Eds.), Mycotoxins in Agriculture and Food Safety, Eastern Hemisphere Distribution. Marcel Dekker, New York, 1998;pp:381-405.
  34. Rahmani A, Jinap S, Soleimany F. Qualitative and Quantitative Analysis of Mycotoxins. Compr Rev Food Sci Food Saf. 2009;8(3):202-51.