Aflatoxins Risk Profile
Aflatoxins are a group of
mycotoxins produced by Aspergillus
flavus and Aspergillus
parasiticus and can cause serious complications in animals and
humans. The four major aflatoxins are AFB1, AFB2, AFG1, and AFG2. These may grow
in a broad range of agricultural commodities including plant leaves, dried
fruit, corns, nuts, and infect stored cereal grains where they produce the
aflatoxins. When such toxins are formed they do not go away. The aflatoxin was
first recognized in damaged peanuts contaminated with Aspergillus flavus. The
aflatoxins are easily identifiable with their blue or green fluorescence under
UV light and relative chromatographic mobility after thin-layer chromatographic
separation. They are heat-stable and thus stay in the food along the food
chain, unaffected by heat treatments such as pasteurization. On the other hand,
aflatoxin AFB1, which is present in contaminated feed or food can be converted
to M1 (AFM1). If a cow eats a feed contaminated with aflatoxin B1, the activity
of the cow changes the aflatoxin B1 to aflatoxin M1, which ends up in the milk
(Johnsson, 2006). Hence, AFM1 in milk is not as hazardous as its parent
compound, but the limit is 0.5 parts per billion, largely because milk tends to
constitute a large part of the diet of infants and children.
The toxicity of aflatoxin is mainly due to its carcinogenicity and the most potent known natural carcinogen is AFB1. This is because aflatoxins are genotoxic, meaning it affects the genetic material. Genotoxins have a direct dose-response relationship, so they do not have a threshold dose to exceed before they have an effect. Thus, there is no tolerable daily intake (TDI) for aflatoxins, which are to be kept at a level as low as possible.
Sources
Disease
Chronic exposure to aflatoxin affects many organs and it critically affects the liver as the body’s detoxification functions are usually taken place in the liver because aflatoxins are hepatotoxic in humans and animals. Long-term aflatoxin exposures from the food products may cause aflatoxicosis, which can range from acute to chronic, and sickness can range from mild to severe. The severe liver damage can lead to cirrhosis, which may lead to the development of liver cancer, but it is usually not possible to prove the damage is caused by aflatoxins, hence test tumor tissue for biomarkers or characteristic genetic damage are the basic possible models.
Mortality:
There are several cases of documented
aflatoxin poisoning around the world including India (1974), Kenya (1982, 2004
and 2005), and Malaysia (1988) resulting in altogether 747 hospitalizations and
258 fatalities. Thus, by far it presences a great danger to humans and animals
in the context of food safety and it is lethal in both acute and chronic
exposures, given the right dose depend on the exposing person’s or animal’s
general health status.
Toxic dose:
The exact toxic dose for a human is
yet unknown, but there are documented records of toxic levels of aflatoxin
ingestions from in the following countries illustrate different mortality rates
from outbreaks:
o
In 1974, there were 397 sufferers and 108 fatalities in
northwest India, where aflatoxin levels of 0.25 to 15 mg/kg were found in corn.
o
In 1982, in Kenya reported 20 hospitalizations with a 60%
mortality rate, with aflatoxin intake of 38 µg/kg of body weight.
o
In 1988, 13 Chinese children died after eating Chinese
noodles in Malaysia, due to acute hepatic encephalopathy, where postmortem
samples from the patients confirmed the presence of aflatoxins.
o
One of the largest aflatoxicosis outbreaks on record
occurred during 2004 and 2005 in rural Kenya, exposing 317 people with 125
fatalities, where the root cause was aflatoxin-contaminated homegrown maize
with an average toxic dose of 354 ng/g.
o
A laboratory worker who intentionally ingested AFB1 at 12
µg/kg body weight for two days has developed a rash, nausea, and headache, but
recovered without ill effect. However, a 14-year follow-up study of the worker
confirmed that physical examination and blood chemistry, including tests for
liver function, were normal.
o
The effects of aflatoxins on the health of the various
animals depend on their species, level, and duration of exposure, including
nutritional status. Thus, the median lethal dose (i.e., LD50) values show wide
variation, ranging from 0.3 mg/kg body weight in rabbits to 18 mg/kg body
weight in rats.
o
Aflatoxins do not affect equally in every animal, but
moderately to highly toxic and carcinogenic in almost every animal species
tested, and their main factor for tolerance relates to the nature of the
digestive system. Other tolerance factors include breed variety, nutrition,
sex, age, environmental stress, and the presence of other disease agents, and
ruminants are more tolerant. But other animals such as swine, chickens, ducks,
pets, and wild birds are more sensitive.
Onset:
Not applicable.
Complications:
Acute exposure to high doses of aflatoxin can result in aflatoxicosis which leads to the damage of the liver where aflatoxin inhibits the normal functions of the liver, including carbohydrate and lipid metabolism and protein synthesis. Cancer, impaired protein formation, impaired blood coagulation, toxic hepatitis, and probable immunosuppression can be resulted from chronic exposure due to substantial doses. There can be reduced weight gain and reduced feed-conversion efficiency in animals apart from the complications. The International Agency for Research on Cancer has classified AFB1 as a group 1 carcinogen and AFM1 as a group 2b carcinogen (carcinogenic to laboratory animals and possibly carcinogenic to humans, respectively), because AFB1 is the most potent known natural carcinogen and is the most abundant of the aflatoxins and they are probably immunosuppressive in humans. Combined exposure to aflatoxin and hepatitis B increases the risk for the development of human hepatocellular carcinoma (HCC) and the diagnosis of chronic aflatoxicosis is difficult without sophisticated laboratory equipment. Aflatoxins are primarily affecting the cellular immune processes and also affect to decrease in antibody formation, embryonic exposure, and reducing immune responses in offspring, in most of the laboratory animal species studied.
Symptoms:
General symptoms include edema of the
lower extremities, abdominal pain, and vomiting in addition to the disruption
and inhibition of carbohydrate and lipid metabolism and protein synthesis
associated with aflatoxicosis in humans can lead to hemorrhaging, jaundice,
premature cell death, tissue necrosis in the liver and, possibly other organs.
Duration:
The duration of symptoms are varied,
but no appropriate scientific data is available.
Route of entry:
Oral.
Pathway:
AFB1 can interact with DNA, leading to structural damages which if not repaired, a mutation can occur that may initiate the cascade of events required to produce cancer. Once activated by cytochrome P450 monooxygenases, AFB1 is metabolized to a highly reactive metabolite, AFB1-exo-8,9-epoxide. Then metabolize binds with the guanine moiety of DNA at the N7 position, forming trans-8,9-dihydro-8-(N7-guanyl)-9 hydoxyAFB1 adducts, which can rearrange and form a stable adduct, and studies have shown that it is associated with tumor cells.
Frequency
Diagnosis
The aflatoxicosis in humans can be diagnosed by Jaundice and its characteristic yellowing of tissues due to the liver damage, as well as gall bladder may become swollen, and immunosuppression may provide an opportunity for secondary infections. There can be a decrease in vitamin K functions and high levels of AFB1-albumin adducts may be present in plasma. Aflatoxin exposure can be identified through biomarkers that detect the presence of metabolites in blood, milk, and urine, and excreted DNA adducts and blood-protein adducts. Further, AFB1-albumin adducts can be measured in blood and converted AFM1 and AFB1-DNA adduct or AFB1-guanine adduct can be subsequently detected in the urine of people consuming sufficient amounts of AFB1.
Food Analysis
The most difficult
step in mycotoxin determination is the sampling due to contaminant variability
and there are developed procedures for sampling, sample preparation,
extraction, purification, isolation, separation, and quantitation of aflatoxins
in foods. The use of proper sampling equipment and techniques can reduce the
effects of sample selection while increasing sample size can reduce the effects
of the distribution of contaminated particles within a lot.
Analytical methods used to identify aflatoxins are usually quantitative or semi-quantitative assays and rapid screening tests, where Thin-layer chromatography (TLC) is among the most widely-used analytical methods. Sample cleanup is a time-consuming step and usually consists of extraction with solvent, liquid-liquid partition, and/or chromatographic separation and determination. The antibody development is another technique that has led to the development of enzyme-linked immunosorbent assays (ELISAs) which are mainly used in screening methods. The high-performance liquid chromatography (LC) with fluorescence detection and hyphenated methods, such as LC/mass spectrometry (MS) or LC/MS-MS, are also used in quantitation and confirmation of identities. The modern analytical technologies evolving for aflatoxin detection includes solid-phase micro-extraction, surface-plasmon resonance, fiber-optic sensors, electrochemical immunosensors, fluorescence-based immunoassays, and the use of molecularly imprinted polymers.
Reference:
FDA Bad Bug Book, Foodborne Pathogenic Microorganisms and Natural Toxins. Second Edition. 2013
Preventive Controls for Human Foods. 2016
www.cdc.gov
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