Aflatoxin

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Chemical structure of aflatoxin B1 (-)-Aflatoxin B1 Structural Formulae V.1.svg
Chemical structure of aflatoxin B1

Aflatoxins are various poisonous carcinogens and mutagens that are produced by certain molds, particularly Aspergillus species mainly by Aspergillus flavus [1] and Aspergillus parasiticus . [2] According to the USDA, "They are probably the best known and most intensively researched mycotoxins in the world." [3] The fungi grow in soil, decaying vegetation and various staple foodstuffs and commodities such as hay, maize, peanuts, coffee, wheat, millet, sorghum, cassava, rice, chili peppers, cottonseed, tree nuts, sesame seeds, sunflower seeds, and various cereal grains and oil seeds. In short, the relevant fungi grow on almost any crop or food. When such contaminated food is processed or consumed, the aflatoxins enter the general food supply. They have been found in both pet and human foods, as well as in feedstocks for agricultural animals. Animals fed contaminated food can pass aflatoxin transformation products into milk, milk products, and meat. [4] For example, contaminated poultry feed is the suspected source of aflatoxin-contaminated chicken meat and eggs in Pakistan. [5]

Contents

Children are particularly vulnerable to aflatoxin exposure, which is linked to immune suppression, stunted growth, [6] delayed development, [7] aflatoxicosis, [8] food spoilage and liver cancer. [9] Some studies have reported an association between childhood stunting and aflatoxin exposure, although this link has not been consistently detected in all studies. [10] [11] but could not be detected in all. [12] [13] Furthermore, a causal relationship between childhood stunting and aflatoxin exposure has yet to be conclusively shown by epidemiological studies, though such investigations are underway. [14] [15] [16] Adults have a higher tolerance to exposure, but are also at risk. No animal species is known to be immune. Aflatoxins are among the most carcinogenic substances known. [17] After entering the body, aflatoxins may be metabolized by the liver to a reactive epoxide intermediate or hydroxylated to become the less harmful aflatoxin M1.

Aflatoxin poisoning most commonly results from ingestion, but the most toxic aflatoxin compound, B1, can permeate through the skin. [18]

The United States Food and Drug Administration (FDA) action levels for aflatoxin present in food or feed is 20 to 300 ppb. [19] The FDA has had occasion to declare both human and pet food recalls as a precautionary measure to prevent exposure.

The term "aflatoxin" is derived from the name of the species Aspergillus flavus, in which some of the compounds first were discovered. A new disease was identified with unknown characteristics in England during the 1950s and 1960s, which increased turkey mortality. Later, aflatoxin was recognized in 1960 in England as a causative agent of the mysterious Turkey ‘X’ disease that causes excessive mortality in turkey poults. [20] [21] Aflatoxins form one of the major groupings of mycotoxins, and apart from Aspergillus flavus various members of the group of compounds occur in species such as: Aspergillus parasiticus, Aspergillus pseudocaelatus, Aspergillus pseudonomius, and Aspergillus nomius. [22]

Major types and their metabolites

Aflatoxin B1 is considered the most toxic and is produced by both Aspergillus flavus and Aspergillus parasiticus . Aflatoxin M1 is present in the fermentation broth of Aspergillus parasiticus, but it and aflatoxin M2 are also produced when an infected liver metabolizes aflatoxin B1 and B2.

AFM, AFQ, and AFL retain the possibility to become an epoxide. Nevertheless, they appear much less capable of causing mutagenesis than the unmetabolized toxin. [26]

Contamination conditions

Aflatoxins are produced by both Aspergillus flavus and Aspergillus parasiticus , which are common forms of 'weedy' molds widespread in nature. The presence of those molds does not always indicate that harmful levels of aflatoxin are present, but does indicate a significant risk. The molds can colonize and contaminate food before harvest or during storage, especially following prolonged exposure to a high-humidity environment, or to stressful conditions such as drought. Aflatoxin contamination is increasing in crops such as maize as a result of climate change creating better conditions for these molds. [27] [28]

The native habitat of Aspergillus is in soil, decaying vegetation, hay, and grains undergoing microbiological deterioration, but it invades all types of organic substrates whenever conditions are favorable for its growth. Favorable conditions for production of aflatoxins include high moisture content (at least 7%) and temperatures from 55 °F (13 °C) to 104 °F (40 °C) [optimum 27 to 30 °C (81 to 86 °F)]. [29] [30] Aflatoxins have been isolated from all major cereal crops, and from sources as diverse as peanut butter and cannabis. The staple commodities regularly contaminated with aflatoxins include cassava, chilies, corn, cotton seed, millet, peanuts, rice, sorghum, sunflower seeds, tree nuts, wheat, and a variety of spices intended for human or animal consumption. Aflatoxin transformation products are sometimes found in eggs, milk products, and meat when animals are fed contaminated grains. [4] [31]

A study conducted in Kenya and Mali found that the predominant practices for drying and storage of maize were inadequate in minimizing exposure to aflatoxins. [32]

Organic crops, which are not treated with fungicides, may be more susceptible to contamination with aflatoxins. [33]

Prevention

A primary means of limiting risk from aflatoxins in the food supply is food hygiene in the commercial commodity supply chain, such as rejecting moldy grain for use in food processing plants and testing of batches of ingredients for aflatoxin levels before adding them to the mix. Regulatory agencies such as the FDA set limits on acceptable levels. Grain drying itself, which is necessary for viable combine harvesting in many regions, lays the fundamentals for this effort by preventing stored grain from being too damp in the first place.

There is very limited evidence to show that agricultural and nutritional education can reduce exposure to aflatoxin in low to middle income countries. [34]

Pathology

No animal species is known to be immune to the acute toxic effects of aflatoxins. Adult humans have a high tolerance for aflatoxin exposure and rarely succumb to acute aflatoxicosis, [35] but children are particularly affected, and their exposure can lead to stunted growth and delayed development, in addition to all the symptoms mentioned below. [7]

High-level aflatoxin exposure produces an acute hepatic necrosis (acute aflatoxicosis), resulting later in cirrhosis or carcinoma of the liver. Acute liver failure is made manifest by bleeding, edema, alteration in digestion, changes to the absorption and/or metabolism of nutrients, and mental changes and/or coma. [35]

Chronic, subclinical exposure does not lead to symptoms so dramatic as acute aflatoxicosis. Chronic exposure increases the risk of developing liver and gallbladder cancer, [36] as aflatoxin metabolites may intercalate into DNA and alkylate the bases through epoxide moiety. This is thought to cause mutations in the p53 gene, an important gene in preventing cell cycle progression when there are DNA mutations, or signaling apoptosis (programmed cell death). These mutations seem to affect some base pair locations more than others, for example, the third base of codon 249 of the p53 gene appears to be more susceptible to aflatoxin-mediated mutations than nearby bases. [37] As with other DNA-alkylating agents, Aflatoxin B1 can cause immune suppression, and exposure to it is associated with an increased viral load in HIV positive individuals. [38] [39]

The expression of aflatoxin-related diseases is influenced by factors such as species, age, nutrition, sex, and the possibility of concurrent exposure to other toxins. The main target organ in mammals is the liver, so aflatoxicosis primarily is a hepatic disease. Conditions increasing the likelihood of aflatoxicosis in humans include limited availability of food, environmental conditions that favour mould growth on foodstuffs, and lack of regulatory systems for aflatoxin monitoring and control. [40]

A regular diet including apiaceous vegetables, such as carrots, parsnips, celery, and parsley may reduce the carcinogenic effects of aflatoxin. [41]

There is no specific antidote for aflatoxicosis. Symptomatic and supportive care tailored to the severity of the liver disease may include intravenous fluids with dextrose, active vitamin K, B vitamins, and a restricted, but high-quality protein diet with adequate carbohydrate content.

In other animals

In dogs, aflatoxin has potential to lead to liver disease. Low levels of aflatoxin exposure require continuous consumption for several weeks to months in order for signs of liver dysfunction to appear. [42] Some articles have suggested the toxic level in dog food is 100–300 ppb and requires continuous exposure or consumption for a few weeks to months to develop aflatoxicosis. [43] No information is available to suggest that recovered dogs will later succumb to an aflatoxin-induced disease.

Turkeys are extremely susceptible to aflatoxicosis. Recent studies have revealed that this is due to the efficient cytochrome P450 mediated metabolism of aflatoxin B1 in the liver of turkeys and deficient glutathione-S-transferase mediated detoxification. [44] [45]

Some studies on pregnant hamsters showed a significant relationship between exposure of aflatoxin B1 (4 mg/kg, single dose) and the appearance of developmental anomalies in their offspring. [46]

In 2005, Diamond Pet Foods discovered aflatoxin in a product manufactured at their facility in Gaston, South Carolina. [47] [48] In 23 states, Diamond voluntarily recalled 19 products formulated with corn and manufactured in the Gaston facility. Testing of more than 2,700 finished product samples conducted by laboratories confirmed that only two date codes of two adult dog formulas had the potential to be toxic. [49]

In December 2020 and January 2021, Midwestern Pet Foods recalled dog food that contained fatal levels of aflatoxin. [50] As many as 70 dogs had died from aflatoxin poisoning by January 12, 2021. [51]

Detection in humans

There are two principal techniques that have been used most often to detect levels of aflatoxin in humans.

The first method is measuring the AFB1-guanine adduct in the urine of subjects. The presence of this breakdown product indicates exposure to aflatoxin B1 during the past 24 hours. This technique measures only recent exposure, however. Due to the half-life of this metabolite, the level of AFB1-guanine measured may vary from day to day, based on diet, it is not ideal for assessing long-term exposure.

Another technique that has been used is a measurement of the AFB1-albumin adduct level in the blood serum. This approach provides a more integrated measure of exposure over several weeks or months.

List of outbreaks

Aflatoxin timeline from 1960-2021 Aflatoxin timeline.tif
Aflatoxin timeline from 1960-2021

International sources of commercial peanut butter, cooking oils (e.g. olive, peanut and sesame oil), and cosmetics have been identified as contaminated with aflatoxin. [53] [54] [55] In some instances, liquid chromatography–tandem mass spectrometry (LC–MS/MS), and other analytical methods, revealed a range from 48% to 80% of selected product samples as containing detectable quantities of aflatoxin. In many of these contaminated food products, the aflatoxin exceeded the safe limits of the U.S. Food and Drug Administration (FDA), or other regulatory agency. [54] [55] [56]

See also

Resources

  1. ↑ Ramdas Kodape, Anup; Raveendran, Ashika; Shivegowda Vivek Babu, Chikkarasanahalli (2022-11-30), Claude Assaf, Jean (ed.), "Aflatoxins: A Postharvest Associated Challenge and Mitigation Opportunities", Aflatoxins - Occurrence, Detection and Novel Detoxification Strategies, IntechOpen, doi: 10.5772/intechopen.106333 , ISBN   978-1-80356-884-3 , retrieved 2024-04-02
  2. ↑ Ramdas Kodape, Anup; Raveendran, Ashika; Shivegowda Vivek Babu, Chikkarasanahalli (2022-11-30), Claude Assaf, Jean (ed.), "Aflatoxins: A Postharvest Associated Challenge and Mitigation Opportunities", Aflatoxins - Occurrence, Detection and Novel Detoxification Strategies, IntechOpen, doi: 10.5772/intechopen.106333 , ISBN   978-1-80356-884-3 , retrieved 2024-04-02
  3. ↑ https://www.fsis.usda.gov/food-safety/safe-food-handling-and-preparation/food-safety-basics/molds-food-are-they-dangerous
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  5. ↑ Iqbal SZ, et al. (2014). "Natural incidence of aflatoxins, ochratoxin A and zearalenone in chicken meat and eggs". Food Control. 43: 98–103. doi:10.1016/j.foodcont.2014.02.046.
  6. ↑ Khlangwiset P, Shephard GS, Wu F (October 2011). "Aflatoxins and growth impairment: a review". Critical Reviews in Toxicology. 41 (9): 740–55. doi:10.3109/10408444.2011.575766. PMID   21711088. S2CID   19262759.
  7. 1 2 Abbas HK (2005). Aflatoxin and Food Safety. CRC Press. ISBN   978-0-8247-2303-3.
  8. ↑ "Aflatoxicosis". 30 September 2014.
  9. ↑ Kodape, Anup; Lama, Ankita; Vivek Babu, C.S. (April 2024). "Metagenomic insights of fungal diversity of peanuts under storage conditions and mitigation of aflatoxigenic fungi through competitive exclusion and phytochemicals". Food Bioscience. 58: 103711. doi:10.1016/j.fbio.2024.103711.
  10. ↑ Voth-Gaeddert LE, Stoker M, Torres O, Oerther DB (April 2018). "Association of aflatoxin exposure and height-for-age among young children in Guatemala". International Journal of Environmental Health Research. 28 (3): 280–292. Bibcode:2018IJEHR..28..280V. doi:10.1080/09603123.2018.1468424. PMID   29706087. S2CID   23510545.
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  47. ↑ FDA Inspection Report-Diamond Gaston SC Plant 12/21/2005-1/19/2006.
  48. ↑ 2005 Recall, FDA
  49. ↑ AKC Standard Article Contaminated Diamond Pet Food Products and 'Best By' Dates Narrowed Akcstandard.com Archived July 7, 2011, at the Wayback Machine
  50. ↑ Medicine, Center for Veterinary (2021-01-12). "FDA Alert: Certain Lots of Sportmix Pet Food Recalled for Potentially Fatal Levels of Aflatoxin". FDA.
  51. ↑ Tyko, Kelly. "Dog food recall expands: More than 70 dogs have died and 80 pets sick after eating Sportsmix pet food". USA TODAY. Retrieved 2021-01-13.
  52. ↑ Ramdas Kodape, Anup; Raveendran, Ashika; Shivegowda Vivek Babu, Chikkarasanahalli (2022-11-30), Claude Assaf, Jean (ed.), "Aflatoxins: A Postharvest Associated Challenge and Mitigation Opportunities", Aflatoxins - Occurrence, Detection and Novel Detoxification Strategies, IntechOpen, doi: 10.5772/intechopen.106333 , ISBN   978-1-80356-884-3 , retrieved 2024-04-10
  53. ↑ Bao L, Trucksess MW, White KD (2010). "Determination of aflatoxins B1, B2, G1, and G2 in olive oil, peanut oil, and sesame oil". Journal of AOAC International. 93 (3): 936–42. doi: 10.1093/jaoac/93.3.936 . PMID   20629398.
  54. 1 2 Li FQ, Li YW, Wang YR, Luo XY (May 2009). "Natural occurrence of aflatoxins in Chinese peanut butter and sesame paste". Journal of Agricultural and Food Chemistry. 57 (9): 3519–24. doi:10.1021/jf804055n. PMID   19338351.
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  57. ↑ Staff (19 May 2014). "Gdy otwarto grób królewski, zaczęła działać klątwa Jagiellończyka" [When the royal tomb was opened, the Jagiellon curse began its work]. Gazeta Krakowska. Retrieved 18 January 2023.
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Aspergillus is a genus consisting of several hundred mold species found in various climates worldwide.

<span class="mw-page-title-main">Fumonisin B1</span> Chemical compound

Fumonisin B1 is the most prevalent member of a family of toxins, known as fumonisins, produced by multiple species of Fusarium molds, such as Fusarium verticillioides, which occur mainly in maize (corn), wheat and other cereals. Fumonisin B1 contamination of maize has been reported worldwide at mg/kg levels. Human exposure occurs at levels of micrograms to milligrams per day and is greatest in regions where maize products are the dietary staple.

<span class="mw-page-title-main">Trichothecene</span> Large family of chemically related mycotoxins

The trichothecenes are a large family of chemically related mycotoxins. They are produced by various species of Fusarium, Myrothecium, Trichoderma/Podostroma, Trichothecium, Cephalosporium, Verticimonosporium, and Stachybotrys. Chemically, trichothecenes are a class of sesquiterpenes.

<span class="mw-page-title-main">Cyclopiazonic acid</span> Chemical compound

Cyclopiazonic acid (α-CPA), a mycotoxin and a fungal neurotoxin, is made by the molds Aspergillus and Penicillium. It is an indole-tetramic acid that serves as a toxin due to its ability to inhibit calcium-dependent ATPases found in the endoplasmic and sarcoplasmic reticulum. This inhibition disrupts the muscle contraction-relaxation cycle and the calcium gradient that is maintained for proper cellular activity in cells.

Hermetic storage is a method of using sealed, airtight units to control moisture and insects in stored dry agricultural commodities. The hermetic storage restricts gas exchanges between the internal and external environments and the stored commodity, maintaining the initial levels of moisture and controlling pests by the lack of oxygen.

<span class="mw-page-title-main">Oncom</span> Indonesian traditional fermented dish

Oncom is one of the traditional staple foods of the Sundanese cuisine of Indonesia. There are two kinds of oncom: red oncom and black oncom. Oncom is closely related to tempeh; both are foods fermented using mold.

Mycotoxicology is the branch of mycology that focuses on analyzing and studying the toxins produced by fungi, known as mycotoxins. In the food industry it is important to adopt measures that keep mycotoxin levels as low as practicable, especially those that are heat-stable. These chemical compounds are the result of secondary metabolism initiated in response to specific developmental or environmental signals. This includes biological stress from the environment, such as lower nutrients or competition for those available. Under this secondary path the fungus produces a wide array of compounds in order to gain some level of advantage, such as incrementing the efficiency of metabolic processes to gain more energy from less food, or attacking other microorganisms and being able to use their remains as a food source.

<span class="mw-page-title-main">Sterigmatocystin</span> Chemical compound

Sterigmatocystin is a polyketide mycotoxin produced by certain species of Aspergillus. The toxin is naturally found in some cheeses.

Pathogenic fungi are fungi that cause disease in humans or other organisms. Although fungi are eukaryotic, many pathogenic fungi are microorganisms. Approximately 300 fungi are known to be pathogenic to humans; their study is called "medical mycology". Fungal infections are estimated to kill more people than either tuberculosis or malaria—about two million people per year.

Microbial toxins are toxins produced by micro-organisms, including bacteria, fungi, protozoa, dinoflagellates, and viruses. Many microbial toxins promote infection and disease by directly damaging host tissues and by disabling the immune system. Endotoxins most commonly refer to the lipopolysaccharide (LPS) or lipooligosaccharide (LOS) that are in the outer plasma membrane of Gram-negative bacteria. The botulinum toxin, which is primarily produced by Clostridium botulinum and less frequently by other Clostridium species, is the most toxic substance known in the world. However, microbial toxins also have important uses in medical science and research. Currently, new methods of detecting bacterial toxins are being developed to better isolate and understand these toxins. Potential applications of toxin research include combating microbial virulence, the development of novel anticancer drugs and other medicines, and the use of toxins as tools in neurobiology and cellular biology.

Aflatoxin B<sub>1</sub> Chemical compound

Aflatoxin B1 is an aflatoxin produced by Aspergillus flavus and A. parasiticus. It is a very potent carcinogen with a TD50 3.2 μg/kg/day in rats. This carcinogenic potency varies across species with some, such as rats and monkeys, seemingly much more susceptible than others. Aflatoxin B1 is a common contaminant in a variety of foods including peanuts, cottonseed meal, corn, and other grains; as well as animal feeds. Aflatoxin B1 is considered the most toxic aflatoxin and it is highly implicated in hepatocellular carcinoma (HCC) in humans. In animals, aflatoxin B1 has also been shown to be mutagenic, teratogenic, and to cause immunosuppression. Several sampling and analytical methods including thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), mass spectrometry, and enzyme-linked immunosorbent assay (ELISA), among others, have been used to test for aflatoxin B1 contamination in foods. According to the Food and Agriculture Organization (FAO), a division of the United Nations, the worldwide maximum tolerated levels of aflatoxin B1 was reported to be in the range of 1–20 μg/kg (or .001 ppm - 1 part-per-billion) in food, and 5–50 μg/kg (.005 ppm) in dietary cattle feed in 2003.

Many species of fungi produce secondary metabolites called mycotoxins. These toxins can be very detrimental to both humans and animals. The side-effects of ingesting these toxic substances are called mycotoxicosis, which can be a variety of medical conditions. The most common fungi that produce mycotoxins include Fusarium, Aspergillus, and Penicillium.

Aspergillus ochraceus is a mold species in the genus Aspergillus known to produce the toxin ochratoxin A, one of the most abundant food-contaminating mycotoxins, and citrinin. It also produces the dihydroisocoumarin mellein. It is a filamentous fungus in nature and has characteristic biseriate conidiophores. Traditionally a soil fungus, has now began to adapt to varied ecological niches, like agricultural commodities, farmed animal and marine species. In humans and animals the consumption of this fungus produces chronic neurotoxic, immunosuppressive, genotoxic, carcinogenic and teratogenic effects. Its airborne spores are one of the potential causes of asthma in children and lung diseases in humans. The pig and chicken populations in the farms are the most affected by this fungus and its mycotoxins. Certain fungicides like mancozeb, copper oxychloride, and sulfur have inhibitory effects on the growth of this fungus and its mycotoxin producing capacities.

<i>Aspergillus parasiticus</i> Species of fungus

Aspergillus parasiticus is a fungus belonging to the genus Aspergillus. This species is an unspecialized saprophytic mold, mostly found outdoors in areas of rich soil with decaying plant material as well as in dry grain storage facilities. Often confused with the closely related species, A. flavus, A. parasiticus has defined morphological and molecular differences. Aspergillus parasiticus is one of three fungi able to produce the mycotoxin, aflatoxin, one of the most carcinogenic naturally occurring substances. Environmental stress can upregulate aflatoxin production by the fungus, which can occur when the fungus is growing on plants that become damaged due to exposure to poor weather conditions, during drought, by insects, or by birds. In humans, exposure to A. parasiticus toxins can cause delayed development in children and produce serious liver diseases and/or hepatic carcinoma in adults. The fungus can also cause the infection known as aspergillosis in humans and other animals. A. parasiticus is of agricultural importance due to its ability to cause disease in corn, peanut, and cottonseed.

Aflatoxin M<sub>1</sub> Chemical compound

Aflatoxin M1 is a chemical compound of the aflatoxin class, a group of mycotoxins produced by three species of Aspergillus – Aspergillus flavus, Aspergillus parasiticus, and the rare Aspergillus nomius – which contaminate plant and plant products.

John Ingram Pitt was an Australian mycologist, known as a leading expert on the role of fungi in food spoilage. He gained an international reputation as a pioneering researcher on the ecology of spoilage molds in extreme environments.

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