shopify analytics ecommerce



Aflatoxins were initially isolated and identified as the causative toxins in Turkey X disease (necrosis of the liver) in 1960 when over 100,000 turkeys died in England (Asao, 1963). They are the most studied mycotoxins with over 5,000 research papers published through 2002. There are four generally recognized Aflatoxins designated B1, B2, G1 and G2 (Figures 1 and 2). 

The metabolites, M1 & M2, are found in milk (Thirumala-Devi et al (2002). 

The order of toxicity is B1 greater than G1, greater than G2, greater than B2. (IARC, 1976). However, Aflatoxin B1 is the major mycotoxin produced by most species under culture conditions (Ciegler & Bennet, 1980). Because of this and its toxicity, B1 is the most frequently studied of the four.

Aflatoxins are produced by different species of Aspergillus, particularly flavus, oryzae, fumigatus and parasiticus, as well as members of the genera Penicillium (El-Naghy et al, 1991; Searle 1976; Aflatoxins 2002). Strains of Aspergillus flavus and parasiticus produce mycotoxins under favorable conditions. 

Aflatoxins can contaminate corn, cereals, sorghum, peanuts and other oil-seed crops. Thus, food contamination by this group of mycotoxins has been implicated in both animal and human Aflatoxicosis. 

In addition, inhalation of aflatoxins is associated with disease and injury in both animals and humans. Finally, aflatoxins are known animal carcinogens and have been linked to cancer of the liver in humans and kidneys in rodents (Markow et al, 1973; Epstein et al, 1969; Sun et al, 2001; Wild & Turner, 2002).

Aflatoxins and Cancer in Humans

Aflatoxins are carcinogenic to humans and animals. Overall summary evaluation of carcinogenic risk to humans is Group 1 (IARC, 1976; Searle, 1976; Dominguez-Malagon & Gaytan-Graham (2001).

Aflatoxin B1 is a potent liver carcinogen in a variety of experimental animals. It causes liver tumors in mice, rats, fish, marmosets, tree shrews and monkeys following administration by various routes. Types of cancers described in research animals include hepatocellular carcinoma (rats), colon and kidney (rats), cholangiocellular cancer (hamsters), lung adenomas (mice), and osteogenic sarcoma, adenocarcinoma of the gall bladder and carcinoma of the pancreas (monkeys) (IARC, 1976).

In humans, Aflatoxin B1 has been linked to hepatocellular carcinoma from three studies reported in the medical literature, as follows:

An increased incidence (10 % excess) of hepatocellular carcinoma was reported in the southeastern portion of the U.S. in areas of high daily intake of Aflatoxin B1. The daily intake of B1 in the southeastern subjects was 13-197 ug/kg body weight as compared to those in northern and western areas with a daily intake of 0.2-0.3 ug/kg body weight (IARC, 1987).

In China, a strong correlation between the intake of peanut, peanut oil and corn and increased mortality rates for liver cancer were reported in five groups of inhabitants from four villages. The mortality rates were 125, 97.40, 41.65, 24.01 and 1.05, respectively. The median intake of aflatoxin B1 for each group was 6.05, 6.36, 2.69, 1.83 and 0 ug/day. The median daily urine concentrations of M1 metabolite were 16.46, 8, 29, 4.78 and 1.21 ng/person. A significant correlation was found between the mortality rates of primary liver cancer and intake of aflatoxin B1. Further, analysis of M1 in the urine can be used as an index for human exposure to aflatoxin B1 in an epidemiological study (Aflatoxins, 2002).

Cancer in 67 men who had inhaled particles contaminated with aflatoxin were reported in an 11-year follow up study. They worked in a mill crushing peanuts and other oil seeds. Two of the men developed fatal liver disease, while eleven developed cancers of various organs. The 13 men had inhaled doses estimated to be between 160 to 395 ug/cubic meter/man/wk. In 55 matched control men, 4 developed cancer and none died from liver disease. The excess cancers in this study was not significant, however the number of subjects was insufficient to exclude a significant positive correlation (Aflatoxins, 2002; IARC,1976).

Finally, it was reported that in hepatocellular carcinoma cases exposed to aflatoxin B1, mutation of p53 gene is fixed at codon 249 third base and takes the form of G to T transversion. It appears from the reported observations that it is a definite marker of mutation, which is induced by aflatoxin B1 mutagen and is applicable for molecular epidemiology survey of sufferers of aflatoxin B1 exposure among hepatocellular carcinoma cases (Deng & Ma, 1998).

Aflatoxicosis in Humans

Suspected cases of Aflatoxicosis have been reported in India. Over 200 villages in western India experienced an outbreak of disease affecting humans and dogs. The illness was characterized by jaundice, rapidly developing ascites, portal hypertension and a high mortality rate. Death usually occurred from massive gastrointestinal bleeding. The disease was confined to the very poor who ate badly molded corn containing aflatoxin at a concentration of 6.25 to 15.6 ppm. The average daily intake was 1-6 mg of aflatoxin (Aflatoxins, 2002; Keeler et al, 1983).

Reye's syndrome is characterized by symptoms of encephalopathy and fatty degeneration of the viscera. It occurs in children under 16 and is believed to follow nonspecific viral illness, influenza B and varicella. Abnormalities are present in mitochondrial structure and function, including defective oxidative phosphorylation (Stein, 1990). 

Aflatoxins have been reported to be associated with a Reye's-like Syndrome in Thailand, New Zealand, Czechoslovakia, the United States (Aflatoxins, 2002; Ryan et al (1979) Malaysia (Chao, 1991), Venezuela (Burggera, 1986) and Europe (Dvorackova et al, 1977, Stora et al, 1983). 

An incident of 106 fatal cases of hepatic disease among 397 individuals who became ill after eating maize contaminated with aflatoxin also suggests that acute aflatoxicosis can occur in human beings (Haddad, 1990).  Recently, outbreaks of aflatoxicosis resulting from contaminated grain occurred in Kenya (Azziz-Baumgartner et al, 2005; Lewis et al, 2005).

Post-weaning exposure to aflatoxin-contaminated maize has resulted in impaired growth of African children consuming the grain vs infants still being breast fed.  

Aflatoxin concentration mean values were 40.4, 10.1, 8.7 pico grams/mg in maternal, cord and infant blood. In utero exposure also resulted in growth faltering in Gambian infants (Gong et al, 2004; Turner et al, 2007).

The Reye's-like syndrome reported in various places around the world was characterized by multiple symptoms and clinical findings that included disturbed consciousness, fever, convulsions, vomiting, disturbed respiratory rhythm, altered muscle tone and altered reflexes. Serum glutamic-pyruvic transaminase and glutamic-oxalacetic acid transaminase (mitochondrial) enzymes levels were elevated. Hypoglycemia and low cerebrospinal fluid glucose were observed. The onset of the illness included coughing, rhinorrhea, sore throat, earache, slightly enlarged, firm yellow liver, and a pale, slightly widened renal cortex. A high rate of mortality occurred in 81 % of the diagnosed cases. 

Since Reye's Syndrome is characterized by abnormal mitochondrial structure and function, it is of interest to note that aflatoxin B1 causes abnormal mitochondrial structure and function (Shanks et al, 1986; Rainbow et al, 1994; Obasi. 2001; Pasupathy et al, 1999; Sajan et al, 1996).

Aflatoxins have been demonstrated in human cord blood and sera of women immediately after birth. These results demonstrated the transplacental transfer and concentration of aflatoxin by the fetal-placental unit (Aflatoxins, 2002; Turner et al, 2007). Moreover, neonates with and without jaundice were investigated for the presence of aflatoxins in the cord blood. Jaundice and decreased birth weight were correlated with a higher concentration of aflatoxin B1. The observations showed that neonates are exposed to aflatoxin prenatally and that high incidence of jaundice occurred in wet warm months (Abulu et al, 1998). These observations are of biological significance for humans because aflatoxins are mutagenic, carcinogenic, teratogenic and immunosuppressive in animals. The implications of these findings are potentially profound and deserve further study (Aflatoxins, 2002)

Three cases of pulmonary interstitial fibrosis, two agricultural workers and one textile worker, with exposure to aflatoxins have been reported (Dvorackova & Pichova, 1986). Lung samples from the three workers contain aflatoxin B1 suggesting a possible occupational exposure of aflatoxin via the respiratory tract and lung disease.

Immune Response in Humans and Aflatoxins

Antibodies to aflatoxin B1 have been reported in humans. At present, these antibodies are considered indicative of exposure and may or may not be related to disease (Ryan et al, 1979; Wang et al, 2001).  

In addition, genetic polymorphism in humans lacking glutathione transferase enzymes, cytochrome CYP3A5 and microsomal epoxide hyrdolase (mEH) enzymes along with dietary intake are associated with increased levels of aflatoxin-albumin adducts. These observations are supportive of the production of antibodies to aflatoxin-albumin adducts. 

When detoxification pathways either lack (null condition) or have mutations in certain enzymes, free radicals increase leading to protein-free radical adducts Chen et al, 2000; Wild et al, 2000; Wojnowski et al, 2004; Dash et al, 2007).

Workers handling animal feed exposed to mycotoxins, including aflatoxins, were examined for alterations in plasma alpha tumor necrosing factor (TNF-alpha). Airborne concentration of aflatoxin was 0.99 ng/m3. Exposed workers had increased levels of TNF-alpha and concomitant changes in serum lactate dehydrogenase isoenzyme activity (Nuntharatanpong et al, 2002).

Aflatoxicosis in Animals

Domestic animals (pets and agricultural), monkeys, laboratory rats and mice have been the subject of a large body of research on the adverse effects of aflatoxins (particularly B1). These effects include adducts and mutations, cancer, immunosuppression, lung injury and birth defects. Also, aflatoxins have been shown to interact with DNA (nuclear and mitochondrial adducts) and polymerases responsible for DNA and RNA synthesis. The literature is voluminous and can be researched through the National Library of Medicine. Thus, aflatoxicosis in animals will be briefly reviewed here.

Aflatoxins are immunosuppressive in a variety of animals making them more susceptible to infection by various microorganisms. The animals include sheep, cattle, mice, rats rabbits, pigs and poultry, among others (Aflatoxins, 2002; Sharma, 1992; Silvott, et al,1997; Dimitri & Gabal, 2996; Jakab et al, 1994).

Aflatoxicosis in horses, cows and dogs has been described. Essentially, the disease process is similar to that seen in humans. However, because of the ability to study animals in more detail in the laboratory, considerable more scientific information has accumulated regarding the course of the disease.

Calves develop a disease that features blindness, circling and falling down, twitching of ears and grinding of teeth. Spasm of the rectum is seen in most cases. Death usually follows within two days of onset of severe clinical signs. Postmortem findings revealed pale, firm and fibrosed liver. Histologically the main liver changes are centrilobular necrosing, bile duct proliferation and veno-occlusive disease. The kidneys are yellow and surrounded by wet fat. Ascites and edema of the mesentery (enteritis) and rectal eversion are common findings.

Other pathological features in cattle are blood coagulation defects which may involve impairment of prothrombin, factors VII and X and possibly factor IX. 

A single dose of aflatoxin causes increases in plasma enzymes (aspartate aminotransferase, lactate dehydrogenase, glutamate dehydrogenase, gamma-glutamyltransferase and alkaline phosphatase and in bilirubin, probably reflecting liver damage. Other abnormal clinical findings are proteinura, ketouria, glycosuria and hematuria (Aflatoxins, 2002). Similar changes in blood coagulation parameters have been reported in dogs (Aflatoxins, 2002).

Domestic dogs are highly susceptible to liver injury. Nine dogs in Tennessee developed liver pathology following the consumption of aflatoxin-tainted dog food (Newman, et al, 2007). Four dogs died and 5 were euthanized after signs of severe liver failure. The contaminated dog food contained 223-579 ppb of aflatoxin B1. Liver autopsy specimens had concentrations of aflatoxin M1 (a metabolite) ranging from 0.6-4.4 ppb. The liver pathology included cirrhosis, lipidosis, portal fibroplasia, and biliary hyperplasia, supporting the diagnosis of toxic insult to the liver.

Horses are more susceptible to the adverse effects of aflatoxins than are cattle. The disease in horses is characterized by decreased feed intake, loss of body weight, liver damage, centrilobular hepatic disease and brain, kidney and heart damage. Behavioral changes before death include belligerence, somnolence, excessive yawning, head pressing, circling, aimless walking and even blindness (Hintz, 1990).

Mitochondrial Damage and Aflatoxins

Damage to mitochondria can lead to mitochondrial diseases and may be responsible for aging mechanisms. The damage can be to mitochondrial DNA (adducts and mutations), mitochondrial membranes and increased cell death (apoptosis), as well as disruption of energy production (production of ATP) (Wallace, 1997; Thrasher, 2000). 

Aflatoxin B1 preferentially attacks mitochondrial DNA (mitDNA) during hepato-carcinogenesis vs nuclear DNA (Niranjan et al, 1982, 1986).  MitDNA is protected in aflatoxicosis resistant rodents from DNA adducts that effect mitochondrial transcription and translation (Meki et al, 2002).  The mycotoxin alters energy-linked functions of ADP phosphorylation and FAD- and NAD-linked oxidizing substrates (Sajan, 1986) and a-ketoglutarate-succinate cytochrome reductases (Obasi, 2002). It causes ultrastructural changes in mitochondria (Shanks et al, 1986; Rainbow et al, 1994);and also induces mitochondrial directed apoptosis (Pasupathy et al, 1999; Meki et al, 2001; Baron et al, 2000). 

Thus, disruption of mitochondria may well lead to dysfunction of various organs and concomitant symptoms that escape standard medical diagnostics. For example, it is believed that certain mitochondrial diseases result from the ability of the nucleus to detect energetic deficits in its area. The nucleus attempts to compensate for the power shortages (e.g., lack of ATP) by triggering the replication of any nearby mitochondria. Unfortunately, this response promotes replication of the very mitochondria that are causing the local energy shortage, further aggravating the problem (see Wallace, 1997 for further detailed information).
Aflatoxins affecting crops

Aflatoxins can infect crops including corn, peanuts, 
coffee beans, rice, wheat, barley and others

Aflatoxin infected corn

Aflatoxin infected corn

Aflatoxin infected peanuts

Aflatoxin infected peanuts

Aflatoxin in pet food

Aflatoxin in pet food


Aflatoxicosis, be it humans or animals, is characterized by liver damage. Based on what information is available with respect to human exposure, encephalopathy can occur and is also observed in domestic animals. In addition, preliminary evidence from human studies demonstrates that aflatoxins cause an increase in circulating alpha tumor necrosing factor, suggesting that these mycotoxins are also immunotoxic in humans. In animals, immunosuppression does occur in a variety of different species.

Aflatoxins are present in the food chain. They have been found in human cord blood and apparently can enter the developing fetus in humans and animals (Hintz, 1990; Denning et al, 1990).

In addition, aflatoxins have been found in human breast milk (El-Nesami HS et al, 1995), cow's milk and dairy products (Srivastava VP et al 2001; Thirumala-Devi et al, 2002) and infant formula (Aksit et al, 1997). Not only has exposure to aflatoxins been implicated in hepatocellular carcinoma, hepatic failure, encephalopathy and Reye's syndrome, such exposure may also be important in the health and well-being of the fetus and neonates. Thus, it has been postulated that intra-uterine and neonate exposure from contaminated food products may play an etiology in (1) Kwashiorkor, (2) neonatal susceptibility to infection and jaundice, (3) childhood infections and malignant disease and compromised response to prophylactic immunizations in children (Hendrickse, 1991).

Finally, aflatoxin B1 can cause mutations to both nuclear and mitochondrial DNA. Albumin-aflatoxin adducts apparently are increased in individuals with genetic polymorphism in association with GSTM1 null, mEH heterozygote and CYP3A5 mutations. 


Abulu EO et al (1998) Preliminary investigation on aflatoxin in cord blood of jaundiced neonates. West Afr J Med 17:184.

Aflatoxins (2002) National Library of Medicine. Hazardous Substance Data Base. Toxnet (National Data Network).

Aksit S et al (1997) Aflatoxin: is it a neglected threat for formula-fed infants? Acta Pediatr 39:34.

Asao T, et al (1963) Aflatoxins B and G. J Amer Chem. Soc 85:1706.

Azziz-Baumgartner E, Lindblade K, et al (2005) Case-Control study of an acute aflatoxicosis outbreak, Kenya 2004. Environ Health Perspec 113:177.

Baron CC et al (2000) Lipopolysaccharide augments aflatoxin B(1)-induced liver injury through neutrophil-dependent and -independent mechanisms. Toxicol Sci 58:208.

Burggera JA (1986) Presence of aflatoxin B1 in human liver referred to as Reye's syndrome. Acta Cient Venez 37:325.

Chao TC et al (1991) An outbreak of Aflatoxicosis and boric acid poisoning in Malaysia: a clinicopathological study. J Pathol 164:225.

Chen SY, Chen CJ et al (2000) Associations of plasma aflatoxin B1-albumin level with plasma selenium level and genetic polymorphism of glutathione s-transferase M1 and T1. Nutr Cancer 38:179-85.

Ciegler AM ,Bennet JW (1980) Mycotoxins and Mycotoxicosis. Bioscience 30:512.

Dash B, Afriyie-Gyawu E, et al (2007) Determinants of the variability of aflatoxin-albumin adduct in levels in Ghanaians. Toxicol Environ Health A 70:58-66. 

Deng ZL, Ma Y (1998). Aflatoxin sufferer and p53 gene mutation in hepatocellular carcinoma. World J Gastroenterol 4:28. 

Denning DW et al (1990) Transplacental transfer of aflatoxin in humans. Carcinogenesis 11:1033.

Dimitri RA, Gabal MA (1996) Immunosuppressant activity of aflatoxin ingestion in rabbits measured by response to Mycobacterium bovis antigen I. Cell mediated immune response measured by skin test reactions. Vet Hum Toxicol 38:333.

Dominguez-Malagon H, Gaytan-Graham S (2001) Hepatocellular carcinoma: an update. Ultrastruct Pathol 25:497.

Dvorackova I et al (1977) Aflatoxin and encephalopathy with fatty degeneration of viscera (Reye). Ann Nutr. Alimet 31:977.

Dvorackova I, Pichova V (1986) Pulmonary interstitial fibrosis with evidence of aflatoxin B1 in lung tissue. Toxicol Environ Health 18:153.

El-Naghy MA, Mazen MB, Fadl-Allah EM (1991) Studies on the fungus flora and aflatoxin production of cotton seeds in Egypt. J Islamic Acad Sci 4:141. 

El-Nesami HS et al (1995) Aflatoxin M1 in human breast milk samples in Victoria, Australia and Thailand. Food Chem. Toxicol 33:173.

Epstein SM, et al (1969) Renal epithelial neoplasms in male Wistar rats by oral Aflatoxin B1. Cancer Res 29:1045.

Gong Y, Hounsa A, et al S, et al (2004) Post weaning exposure to Aflatoxin results in impaired child growth: a longitudinal study in Benin, West Africa. Environ Health Perspec 112:1334.

Hendrickse RG (1991) Clinical implications of food contaminated by aflatoxins. Ann Acad Med Singapore 20:84.

Hintz HF (1990) Molds, mycotoxins, and mycotoxicosis. Vet Clinic N America: Equine Practice 6:419.

IARC (1976) Monographs on the evaluation of the carcinogenic risk of chemicals to man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-Present [Multi-volume work, P. V10 60 * V10 63 (1976)].

Jakab GJ et al (1994) Respiratory aflatoxicosis: suppression of pulmonary and systemic host defenses in rats and mice. Toxicol Appl Pharmacol 125:198.

Keeler, RF, Tu AT (eds) (1983) Handbook of Natural Toxins, Volume 1. Plant and Fungal Toxins. New York: Marcell Dekker, Inc., p. 308.

Lewis L, Onsongo M, et al (2005) Aflatoxin of commercial maize products during an outbreak of acute aflatoxicosis in Eastern and Central Kenya. Environ Health Perspec 223:1763-7.

Markow LP, et al (1973) The ultrastructure of renal neoplasms induced by Aflatoxin B1. Cancer Res 33:1608.

Meki ET et al (2001) Aflatoxin B1 induces apoptosis in rat liver; protective effect of melatonin. Neuroendocrinol 22:417.

Newman SJ, Smith JR, et al (2007). Aflatoxicosis in nine dogs after exposure to contaminated commercial dog food. J Vet Diag Invest 19:168-75.

Niranjan BG et al (1982) Preferential attack of mitochondrial DNA by aflatoxin B1 during hepatocarcinogenesis. Science 215:73.

Niranjan BG et al (1986) Protection of mitochondrial genetic system against aflatoxin B1 binding in animals resistant to aflatoxicosis. Cancer Res 56:3637.

Nuntharatanpong N et al (2001) Increase in tumor necrosing factor-alpha and a change in lactate dehydrogenase isoenzyme pattern in plasma of workers exposed to aflatoxin-contaminated feeds. Arh Hig Rada Toksikol 52:291.

Obasi SC (2001) Effects of scopoletin and aflatoxin B1 on bovine hepatic mitochondrial respiratory complexes, 2: a-ketoglutarate, cytochrome c and succinate cytochrome c reductases. Z Naturforsch [C] 56:278.

Pasupathy K et al (1999) Alterations of phosphatidylinositol signal pathway in hepatic mitochondria following aflatoxin B1 administration. Indian J Exp Biol 47:876.

Rainbow L et al (1994) Ultrastructural changes in murine lymphocytes induced by aflatoxin B1. Mycopathologia 125:33.
Ryan NJ et al (1979) Aflatoxin B1; its role in the etiology of Reye's syndrome. Pediatrics 64:71.

Sajan MP et al (1996) Alteration of energy-linked functions in rat hepatic mitochondria following aflatoxin B1 administration. J Biochem Toxicol 11:2.

Searle CE (Ed.) (1976) Chemical Carcinogens. ACS Monograph, Washington, DC: American Chemical Society.

Shanks ET et al (1986) Tissue distribution and hepatic ultrastructural effects of aflatoxin B1 in Japanese quail. Pol Arch Weter 26:117.

Sharma RP (1993) Immunotoxicity of mycotoxins. J Dairy Sci 76:892.

Silvott L et al (1997) Immunotoxicological effects on piglets of feeding sows diets containing aflatoxins. Vet Rec 141:469.

Srivastava VP et al (2001) Aflatoxin M1 contamination in commercial samples of milk and dairy products in Kuwait. Food Addit Contam 18:993.

Stein JH (ed) (1990) Internal Medicine. Boston, Mass:Little, Brown & Company. p. 514.

Stora C et al (1983) Aflatoxin and Reye's syndrome. J Med 14:47.

Thirumala-Devi K et al (2002) Development and application of an indirect competitive enzyme-linked immunoassay for aflatoxin m(1) in milk and milk-based confectionery. Agric Food Chem 50:933.

Thrasher JD (2000) Are chlorinated pesticides a causation in maternal mitDNA mutations? Arch Environ Health 55:292.

Turner PC, Collinson AC, Cheung UB, et al (2007). Aflatoxin exposure in utero causes growth faltering in Gambian Infants. International J Epidemiol 36:119.

Wallace DC (1997) Mitochondrial DNA in aging and disease. Scientific American, August, pp. 40-47.

Wang JS et al (2001) Development of aflatoxin B1-lysine adduct monoclonal antibody for human exposure studies. Appl Environ Microbiol 67:2712.

Wild CP, Turner PC, Chemin I, et al (2000) Environmental and genetic determinants of aflatoxin-albumin adducts in the Gambia. Int J Cancer 86:1-7.

Wojnowski L, Turner PC, et al (2004) Increased levels of aflatoxin-albumin adducts are associated with CYP3A5 polymorphism in the Gambia, West Africa. Pharmacogenetics 14:691.

Share by: