**4.2 Biological treatment**

Studies using biotechnology to reduce AFB1 levels in contaminated foods fall into two main categories: one that uses plant extracts to degrade AFB1 and the other that inoculates bacterial strains in food substrates. In recent years, natural plant products have attracted much attention as synthetic antibacterial agents because of their biodegradability, biosafety, effectiveness, and regenerability. At the same time, they are conveniently used as an eco-friendly technology for detoxification. Mycotoxins. Many studies have shown that plant essential oils can inhibit the growth of microorganisms and reduce the production of toxins. Bluma et al. showed that the addition of essential oils in corn kernels has a significant effect on the growth rate, hysteresis and accumulation of AFB1 of aflatoxin molds. Depends on water activity, AFB1 concentration and incubation time [40]. In addition to plant essential oils, water extracts of plants can also be used to dissolve AFB1. Another study by Vijayanandraj et al. also demonstrated the effect of different parameters on the detoxification of AFB1 aqueous extracts from different medicinal plants. They concluded that the leaf extract of Vasaka (*Adhatoda vasica* Nees) showed the greatest AFB1 degradation (≥98%) after incubation for 24 hours at 37°C; the A. vasica leaf extract was heated to 100 by high temperature. Celsius for 10 minutes or autoclaved at 121 degrees Celsius, the detoxification ability is significantly reduced; the A. vasica leaf extract is detected by mass spectrometry to the purified alkaloid, which is believed to be the principle of aflatoxin detoxification [41]. Iram et al. showed that *O. basilicum* leaves extract had significant degradation rates for aflatoxins B1 and B2, and the degradation rates were 90.4 and 88.6%, respectively. The structure of the degradation products was identified by mass spectrometry. Most of the products were passed. Formed by removing the double bond on the terminal furan ring and modifying the lactone group, the degradation property is significantly less toxic than AFB1. The plant extract is easy to obtain, cost-effective and bio-safe, and can be directly sprayed with aqueous plant extracts. Simple, does not involve technical knowledge, is a very good source of detoxification [42].

**197**

**4.4 Sorbent additives**

*The Toxification and Detoxification Mechanisms of Aflatoxin B1 in Human: An Update*

In another method, inoculation of the bacterial strain is to reduce AFB1 by physical binding or metabolism of the bacterial strain directly to AFB1. The biodegradation of aflatoxins has yielded some successful attempts, although most are carried out in sterile culture. The microbial degradation of aflatoxin is achieved by the activity of the enzyme, which is capable of decomposing the refractory polyheterocyclic molecules of aflatoxin. Brana et al. showed that *Pleurotus eryngii* can degrade AFB1 [43]. Farzaneh et al. showed that the repair rates of AFB1 by *Bacillus subtilis* UTBSP1 in nutrient broth and pistachio were 85.66 and 95%, respectively [44]. Liu et al. used cellulose bacteria to degrade the degradation ability of AFB1 in cottonseed meal. By improving the fermentation conditions, the degradation rate can reach 83.4% [45]. Carolyna and other studies have shown that AFB1 is combined with bacteria through weak non-covalent and acid. Of the bacteria treated, the binding may be intracellular rather than extracellular [46]. It is well known that lactic acid bacteria can degrade aflatoxins. Bueno et al. showed that lactobacillus and *Saccharomyces cerevisiae* can rapidly remove AFB1. The binding of AFB1 with microorganisms is a rapid process (no more than 1 minute), and this binding forms a reversible complex between the toxin and microbial surface without the need for chemical modification of the toxin [47]. Studies by Flora Oluwafemi et al. showed that AFB1 was significantly reduced (44.5%) in 50 ng/g contaminated corn, while AFB1 was the least reduced (29.9%) in 500 ng/g contaminated corn. Because lactic acid bacteria are non-toxic, they have many benefits for human health, and it is also possible to reduce the level of aflatoxin to a lower toxic dose. Lactic acid bacteria have broad application prospects as biopreservatives for food and feed [48].

Mycotoxins can be removed or reduced chemically, and acids, bases, oxidizing agents, and reducing agents have been shown to destroy or extinguish mycotoxins. Acids are a natural part of foods that are added to the industry to add flavor to the food, and even some acids are used as preservatives or antioxidants. Organic acids in foods can degrade AFB1. AIKO et al. tested the degradation of AFB1 by various organic acids and considered that the effect of lactic acid was most effective in the organic acids tested. Since lactic acid is endogenous in the human body and is present in many foods, lactic acid is considered to be safe. Therefore, lactic acid can be recommended for food processing and as a preservative in fermented foods [49]. Rushing and other studies have shown that under acidic conditions, organic acids and arginine can be mixed to treat contaminated foods, and AFB1 can be rapidly converted to AFB2a-Arg within 20 minutes, reducing toxicity [50–53]. Aly et al. showed that HCL can effectively degrade AFB1 during acid hydrolysis [54]. Alkaline cooking is also used in the commercial to remove AFB1 from corn. Amination under high temperature and pressure conditions can also reduce AFB1 in corn. There are also many studies on the degradation of AFB1 in foods using ozone. Ozone has been reported as an antibacterial agent because it has antibacterial effects against spores and bacteria of fungi, bacteria, viruses, protozoa and fungi, and has a wide range of antibacterial agents. Ozone inhibits or microbial growth by oxidizing cell membranes and cell wall complex processes [55]. Diao et al. showed a significant decrease in AFB1 levels in peanut seeds at 13 and 21 mg/l ozone concentrations [56]. Proctor et al. showed that the use of ozone oxidation can degrade AFB1 in peanuts, and at an increased tempera-

ture of 75°C, AFB1 degradation rate reached 77% in just 10 minutes [57].

The above method of degrading AFB1 is to destroy or reduce the content of AFB1 in food, and the adsorbent is opposite thereto, which prevents AFB1 from

*DOI: http://dx.doi.org/10.5772/intechopen.89221*

**4.3 Chemical treatment**

#### *The Toxification and Detoxification Mechanisms of Aflatoxin B1 in Human: An Update DOI: http://dx.doi.org/10.5772/intechopen.89221*

In another method, inoculation of the bacterial strain is to reduce AFB1 by physical binding or metabolism of the bacterial strain directly to AFB1. The biodegradation of aflatoxins has yielded some successful attempts, although most are carried out in sterile culture. The microbial degradation of aflatoxin is achieved by the activity of the enzyme, which is capable of decomposing the refractory polyheterocyclic molecules of aflatoxin. Brana et al. showed that *Pleurotus eryngii* can degrade AFB1 [43]. Farzaneh et al. showed that the repair rates of AFB1 by *Bacillus subtilis* UTBSP1 in nutrient broth and pistachio were 85.66 and 95%, respectively [44]. Liu et al. used cellulose bacteria to degrade the degradation ability of AFB1 in cottonseed meal. By improving the fermentation conditions, the degradation rate can reach 83.4% [45]. Carolyna and other studies have shown that AFB1 is combined with bacteria through weak non-covalent and acid. Of the bacteria treated, the binding may be intracellular rather than extracellular [46]. It is well known that lactic acid bacteria can degrade aflatoxins. Bueno et al. showed that lactobacillus and *Saccharomyces cerevisiae* can rapidly remove AFB1. The binding of AFB1 with microorganisms is a rapid process (no more than 1 minute), and this binding forms a reversible complex between the toxin and microbial surface without the need for chemical modification of the toxin [47]. Studies by Flora Oluwafemi et al. showed that AFB1 was significantly reduced (44.5%) in 50 ng/g contaminated corn, while AFB1 was the least reduced (29.9%) in 500 ng/g contaminated corn. Because lactic acid bacteria are non-toxic, they have many benefits for human health, and it is also possible to reduce the level of aflatoxin to a lower toxic dose. Lactic acid bacteria have broad application prospects as biopreservatives for food and feed [48].

### **4.3 Chemical treatment**

*Aflatoxin B1 Occurrence, Detection and Toxicological Effects*

the food with radiation before the mold produces toxins [39].

Studies using biotechnology to reduce AFB1 levels in contaminated foods fall into two main categories: one that uses plant extracts to degrade AFB1 and the other that inoculates bacterial strains in food substrates. In recent years, natural plant products have attracted much attention as synthetic antibacterial agents because of their biodegradability, biosafety, effectiveness, and regenerability. At the same time, they are conveniently used as an eco-friendly technology for detoxification. Mycotoxins. Many studies have shown that plant essential oils can inhibit the growth of microorganisms and reduce the production of toxins. Bluma et al. showed that the addition of essential oils in corn kernels has a significant effect on the growth rate, hysteresis and accumulation of AFB1 of aflatoxin molds. Depends on water activity, AFB1 concentration and incubation time [40]. In addition to plant essential oils, water extracts of plants can also be used to dissolve AFB1. Another study by Vijayanandraj et al. also demonstrated the effect of different parameters on the detoxification of AFB1 aqueous extracts from different medicinal plants. They concluded that the leaf extract of Vasaka (*Adhatoda vasica* Nees) showed the greatest AFB1 degradation (≥98%) after incubation for 24 hours at 37°C; the A. vasica leaf extract was heated to 100 by high temperature. Celsius for 10 minutes or autoclaved at 121 degrees Celsius, the detoxification ability is significantly reduced; the A. vasica leaf extract is detected by mass spectrometry to the purified alkaloid, which is believed to be the principle of aflatoxin detoxification [41]. Iram et al. showed that *O. basilicum* leaves extract had significant degradation rates for aflatoxins B1 and B2, and the degradation rates were 90.4 and 88.6%, respectively. The structure of the degradation products was identified by mass spectrometry. Most of the products were passed. Formed by removing the double bond on the terminal furan ring and modifying the lactone group, the degradation property is significantly less toxic than AFB1. The plant extract is easy to obtain, cost-effective and bio-safe, and can be directly sprayed with aqueous plant extracts. Simple, does not involve technical knowledge, is a very good source of detoxification [42].

**4.2 Biological treatment**

of the steam. Using autoclave cooking in rice can reduce AFB1 levels by 72–83%. The high-pressure cooking method is low in cost and easy to handle, and one of the challenges it faces is how to ensure the integrity of the food after heating. To ensure the integrity of the food, the use of maximum temperatures is often limited [35, 36]. The gamma ray has a strong penetrating electromagnetic wave that can penetrate the material without leaving any residue, which is its advantage. There have been many reports of the increase, decrease, or even unaffected mycotoxin produced by fungi under different conditions. Studies have shown that the fungal structure on paper with a minimum radiation dose of 16 kGy has been altered to avoid fungal growth. Library and file management staff use gamma radiation protection technology to provide a powerful means for the preservation of ancient books, archives and other paper materials [37]. A dose of gamma radiation exceeding 10 kGy can inhibit the germination of peanut seeds. Therefore, proper drying, packaging and environmental control measures with low relative humidity can reduce the growth of fungi and ensure safe, high quality peanuts [38]. The DI Stefano study showed that a radiation dose of 0.5–15 KGy resulted in a decrease in aflatoxin levels in the feed, while a 15 kGy gamma ray did not completely destroy ochratoxin A and aflatoxin in the test feed, FAO/International The IAEA/WHO Expert Committee on Food Irradiation has concluded in its report that foods with an average radiation dose of 10 kGy will not cause toxicological hazards and that toxicologically tested foods do not require retreatment. It is necessary to irradiate

**196**

Mycotoxins can be removed or reduced chemically, and acids, bases, oxidizing agents, and reducing agents have been shown to destroy or extinguish mycotoxins. Acids are a natural part of foods that are added to the industry to add flavor to the food, and even some acids are used as preservatives or antioxidants. Organic acids in foods can degrade AFB1. AIKO et al. tested the degradation of AFB1 by various organic acids and considered that the effect of lactic acid was most effective in the organic acids tested. Since lactic acid is endogenous in the human body and is present in many foods, lactic acid is considered to be safe. Therefore, lactic acid can be recommended for food processing and as a preservative in fermented foods [49]. Rushing and other studies have shown that under acidic conditions, organic acids and arginine can be mixed to treat contaminated foods, and AFB1 can be rapidly converted to AFB2a-Arg within 20 minutes, reducing toxicity [50–53]. Aly et al. showed that HCL can effectively degrade AFB1 during acid hydrolysis [54]. Alkaline cooking is also used in the commercial to remove AFB1 from corn. Amination under high temperature and pressure conditions can also reduce AFB1 in corn. There are also many studies on the degradation of AFB1 in foods using ozone. Ozone has been reported as an antibacterial agent because it has antibacterial effects against spores and bacteria of fungi, bacteria, viruses, protozoa and fungi, and has a wide range of antibacterial agents. Ozone inhibits or microbial growth by oxidizing cell membranes and cell wall complex processes [55]. Diao et al. showed a significant decrease in AFB1 levels in peanut seeds at 13 and 21 mg/l ozone concentrations [56]. Proctor et al. showed that the use of ozone oxidation can degrade AFB1 in peanuts, and at an increased temperature of 75°C, AFB1 degradation rate reached 77% in just 10 minutes [57].

#### **4.4 Sorbent additives**

The above method of degrading AFB1 is to destroy or reduce the content of AFB1 in food, and the adsorbent is opposite thereto, which prevents AFB1 from entering the intestinal tract after ingestion by binding to AFB1, so as to prevent hepatotoxicity of AFB1. Novasil clay minerals and aflatoxins are highly affinitive and high-capacity combinations in the gastrointestinal tract. The study of NS has been shown to absorb AFB1 in vitro in both animal models and human studies, reducing the bioavailability of blood toxins, and its use in humans has not affected the utilization of vitamins and trace elements in the body, and has been determined through clinical trials. A safe dose of NS, a NS content of up to 2.0% (w/w) in the diet does not cause significant toxicity [58–62]. Xue and other studies have shown that the enteral nutrient NovaSil can effectively regulate the toxicity and carcinogenicity of co-exposure to AFB1 and fumonisin B1. When the concentration in the diet is as high as 0.5%, liver changes, liver glutathione S The number and size of -transferase (GST-P+) foci were significantly reduced [63]. Another commonly used binder is chlorophyll. Studies in mammals and fish have shown that chlorophyll can inhibit the formation of carcinogens through the combination of AFB1, reduce the bioavailability of tissues, reduce DNA adduction, and reduce the incidence of tumors [64]. Smimonich observed in the study that after adding chlorophyll to the contaminated AFB1 feed, the AFB1-DNA adduct was reduced by 42%, and the AFB1 albumin adduct was reduced by 65%. AFB n7 - guanine Urinary adducts are reduced by 90%. In the same study, it was also shown that chlorophyll reduced the volume of GSTP lesions in the liver by 74% and the mean number of abnormal crypt lesions in the colon by 63%. Studies have shown that chlorophyll can be used as an early biochemical and advanced pathophysiological marker for AFB1 carcinogenesis in the liver and colon [65].

### **4.5 DNA repair**

In China, HCC is a common malignant tumor with a very poor prognosis, accounting for 55% of the world's HCC cases and more than 340,000 cases per year. This area of tumor-prone is mainly concentrated in eastern and southeastern China. Clinical epidemiological studies have shown that exposure to AFB1 and/or chronic infection with HBV and HCV is a major risk factor for liver cancer. Studies on the toxicity of AFB1 indicate that AFB1 damage to DNA plays a central role in the carcinogenic process of HCC associated with this toxin [48, 66]. AFB1 is metabolized by the cytochrome P450 enzyme into a reactive AFB1-8,9-epoxide (AFB1-epoxide), which is covalently bound to DNA to induce DNA damage. AFB1-induced DNA damage includes AFB1-DNA adducts, oxidative DNA damage, and gene mutations. The AFB1-DNA adduct in AFB1-induced DNA damage is 9-hydroxy afb1 (AFB1-N7- Gua), which is the most common type. The formation of the AFB1-N7-Gua adduct is first performed by pre-covalent insertion of the complex electrophilic between the double-stranded DNA and the high-stranded DNA, and then on the imidazole moiety of the formed AFB1-N7-Gua adduct. The charge generates another desired DNA adduct, a ring-opened carboxamide pyridine AFB1 (AFB1-FAPy) adduct. These adducts are capable of forming subsequent anti-repair adducts, dislocations, or lead to error-prone DNA repair, resulting in single-strand breaks (SSBs), doublestrand breaks (DSBs), and base pair substitutions. The mutations caused by AFB1 exposure, the current major research and experiments believe that the P53 gene is closely related, there is a common mutation hotspot at 249 of TP53 (AGG to AGT) codon [11, 23, 25, 48]. However, epidemiological evidence suggests that although many people are exposed to the same level of AFB1, only a small percentage of the exposed persons have toxicological effects of AFB1, such as genetic mutations and HCC. The Nucleic Acid Excision Repair Pathway (NER), which has been shown to repair aflatoxin-induced DNA adducts, is the major DNA repair pathway. The repair steps of NER are mainly divided into: damage perception, opening denatured

**199**

*The Toxification and Detoxification Mechanisms of Aflatoxin B1 in Human: An Update*

bubbles, cutting damaged chains, transferring damaged oligonucleotides, filling gaps and ligation. There is increasing evidence that genetic polymorphisms in the NER gene are associated with DNA repair capacity and regulate the risk of cancer [66]. In China, molecular epidemiological studies of afb1-related HCC have investigated the association of several genes associated with the NER pathway, such as xeroderma pigmentosum C (XPC) and xeroderma pigmentosum D (XPD). In the oxidative damage of DNA caused by AFB1 exposure, the formation of 8-oxodG is important because it is abundant, highly mutagenic and hepatocarcinogenesis occurs. 8-oxodG lesions are mainly repaired by the BER pathway. The BER pathway promotes DNA repair through two common pathways: a. short patch BER pathway leading to a single nucleotide repair pathway; b. long patch BER pathway, resulting in at least two nucleotide repair pathways. Long et al. first reported DNA repair genes XRCC1, XRCC3, XRCC4, XRCC7, XPD, XPC (including rs25487, rs861539, rs7003908, rs28383151, rs3734091) by analyzing the AFB1-DNA adduct amount, TP53 gene mutation frequency and HCC risk. Genetic polymorphisms of (rs13181, rs2228001) and toxicological effects of AFB1 exposure. Studies have shown that the DNA repair gene XRCC1 gene mutation, XRCC3, XRCC4, XRCC7, XPC, and XPD may increase the AFB1-DNA adduct, the frequency of TP53M, and the risk of hepatocellular carcinoma, genetic mutations with lower DNA repair ability of these genes It should contribute to the toxicological effects of AFB1 and be of a preventive

significance by identifying people with low DNA repair capacity [23, 67, 68].

In developing countries, AFB1 contamination of food is inevitable due to poor environmental and technical conditions, and it is not easy to be treated by high temperature, chemical, physical, etc. Humans can directly use contaminated foods (corn, peanuts, sorghum, rice, cashews, walnuts, pistachios, almonds) or animal products such as milk, eggs, etc. produced by using contaminated animals. The primary hazard of mycotoxin contamination in the food supply chain is human health, followed by animal health and productivity [69, 70]. Every country has strict controls on the mycotoxin contamination of food and feed to reduce human and animal exposure. Currently, Developed countries have access to federal regulatory bodies which set food safety standards and inspect domestic as well as imported/exported food products. Additionally, these countries have access to controlled storage conditions, which greatly reduces contamination post-harvest. These factors lead to lower overall contamination rates in developed countries. For example, the United States has reported acceptable AFB1 levels in corn (0–80 μg/kg during 1979–1983) and low daily intake of its citizens (0.34–197 ng/kg depending on the year and region of the country), which is much less than other undeveloped countries [71]. The European Union (EU) has some of the world's most stringent standards for mycotoxins in food and feed. Compared with the rest of the world, the European Union (EU) has the most extensive and detailed AFB1 presence in various foods and feeds provisions. It has been indicated that in many European countries the presence of AFM1 in milk and milk products was in lower range than the Asian and African countries [72, 73].

AFB1 is a kind of I-type chemical carcinogenic mycotoxin mainly produced by both *A. flavus* and *A. parasiticus* and is known to contaminate most of the world's food supply. AFB1 is the most potent of these compounds and has been well

*DOI: http://dx.doi.org/10.5772/intechopen.89221*

**5. AFB1-related legislation**

**6. Summary and future direction**

*The Toxification and Detoxification Mechanisms of Aflatoxin B1 in Human: An Update DOI: http://dx.doi.org/10.5772/intechopen.89221*

bubbles, cutting damaged chains, transferring damaged oligonucleotides, filling gaps and ligation. There is increasing evidence that genetic polymorphisms in the NER gene are associated with DNA repair capacity and regulate the risk of cancer [66]. In China, molecular epidemiological studies of afb1-related HCC have investigated the association of several genes associated with the NER pathway, such as xeroderma pigmentosum C (XPC) and xeroderma pigmentosum D (XPD). In the oxidative damage of DNA caused by AFB1 exposure, the formation of 8-oxodG is important because it is abundant, highly mutagenic and hepatocarcinogenesis occurs. 8-oxodG lesions are mainly repaired by the BER pathway. The BER pathway promotes DNA repair through two common pathways: a. short patch BER pathway leading to a single nucleotide repair pathway; b. long patch BER pathway, resulting in at least two nucleotide repair pathways. Long et al. first reported DNA repair genes XRCC1, XRCC3, XRCC4, XRCC7, XPD, XPC (including rs25487, rs861539, rs7003908, rs28383151, rs3734091) by analyzing the AFB1-DNA adduct amount, TP53 gene mutation frequency and HCC risk. Genetic polymorphisms of (rs13181, rs2228001) and toxicological effects of AFB1 exposure. Studies have shown that the DNA repair gene XRCC1 gene mutation, XRCC3, XRCC4, XRCC7, XPC, and XPD may increase the AFB1-DNA adduct, the frequency of TP53M, and the risk of hepatocellular carcinoma, genetic mutations with lower DNA repair ability of these genes It should contribute to the toxicological effects of AFB1 and be of a preventive significance by identifying people with low DNA repair capacity [23, 67, 68].

### **5. AFB1-related legislation**

*Aflatoxin B1 Occurrence, Detection and Toxicological Effects*

AFB1 carcinogenesis in the liver and colon [65].

**4.5 DNA repair**

entering the intestinal tract after ingestion by binding to AFB1, so as to prevent hepatotoxicity of AFB1. Novasil clay minerals and aflatoxins are highly affinitive and high-capacity combinations in the gastrointestinal tract. The study of NS has been shown to absorb AFB1 in vitro in both animal models and human studies, reducing the bioavailability of blood toxins, and its use in humans has not affected the utilization of vitamins and trace elements in the body, and has been determined through clinical trials. A safe dose of NS, a NS content of up to 2.0% (w/w) in the diet does not cause significant toxicity [58–62]. Xue and other studies have shown that the enteral nutrient NovaSil can effectively regulate the toxicity and carcinogenicity of co-exposure to AFB1 and fumonisin B1. When the concentration in the diet is as high as 0.5%, liver changes, liver glutathione S The number and size of -transferase (GST-P+) foci were significantly reduced [63]. Another commonly used binder is chlorophyll. Studies in mammals and fish have shown that chlorophyll can inhibit the formation of carcinogens through the combination of AFB1, reduce the bioavailability of tissues, reduce DNA adduction, and reduce the incidence of tumors [64]. Smimonich observed in the study that after adding chlorophyll to the contaminated AFB1 feed, the AFB1-DNA adduct was reduced by 42%, and the AFB1 albumin adduct was reduced by 65%. AFB n7 - guanine Urinary adducts are reduced by 90%. In the same study, it was also shown that chlorophyll reduced the volume of GSTP lesions in the liver by 74% and the mean number of abnormal crypt lesions in the colon by 63%. Studies have shown that chlorophyll can be used as an early biochemical and advanced pathophysiological marker for

In China, HCC is a common malignant tumor with a very poor prognosis, accounting for 55% of the world's HCC cases and more than 340,000 cases per year. This area of tumor-prone is mainly concentrated in eastern and southeastern China. Clinical epidemiological studies have shown that exposure to AFB1 and/or chronic infection with HBV and HCV is a major risk factor for liver cancer. Studies on the toxicity of AFB1 indicate that AFB1 damage to DNA plays a central role in the carcinogenic process of HCC associated with this toxin [48, 66]. AFB1 is metabolized by the cytochrome P450 enzyme into a reactive AFB1-8,9-epoxide (AFB1-epoxide), which is covalently bound to DNA to induce DNA damage. AFB1-induced DNA damage includes AFB1-DNA adducts, oxidative DNA damage, and gene mutations. The AFB1-DNA adduct in AFB1-induced DNA damage is 9-hydroxy afb1 (AFB1-N7- Gua), which is the most common type. The formation of the AFB1-N7-Gua adduct is first performed by pre-covalent insertion of the complex electrophilic between the double-stranded DNA and the high-stranded DNA, and then on the imidazole moiety of the formed AFB1-N7-Gua adduct. The charge generates another desired DNA adduct, a ring-opened carboxamide pyridine AFB1 (AFB1-FAPy) adduct. These adducts are capable of forming subsequent anti-repair adducts, dislocations, or lead to error-prone DNA repair, resulting in single-strand breaks (SSBs), doublestrand breaks (DSBs), and base pair substitutions. The mutations caused by AFB1 exposure, the current major research and experiments believe that the P53 gene is closely related, there is a common mutation hotspot at 249 of TP53 (AGG to AGT) codon [11, 23, 25, 48]. However, epidemiological evidence suggests that although many people are exposed to the same level of AFB1, only a small percentage of the exposed persons have toxicological effects of AFB1, such as genetic mutations and HCC. The Nucleic Acid Excision Repair Pathway (NER), which has been shown to repair aflatoxin-induced DNA adducts, is the major DNA repair pathway. The repair steps of NER are mainly divided into: damage perception, opening denatured

**198**

In developing countries, AFB1 contamination of food is inevitable due to poor environmental and technical conditions, and it is not easy to be treated by high temperature, chemical, physical, etc. Humans can directly use contaminated foods (corn, peanuts, sorghum, rice, cashews, walnuts, pistachios, almonds) or animal products such as milk, eggs, etc. produced by using contaminated animals. The primary hazard of mycotoxin contamination in the food supply chain is human health, followed by animal health and productivity [69, 70]. Every country has strict controls on the mycotoxin contamination of food and feed to reduce human and animal exposure. Currently, Developed countries have access to federal regulatory bodies which set food safety standards and inspect domestic as well as imported/exported food products. Additionally, these countries have access to controlled storage conditions, which greatly reduces contamination post-harvest. These factors lead to lower overall contamination rates in developed countries. For example, the United States has reported acceptable AFB1 levels in corn (0–80 μg/kg during 1979–1983) and low daily intake of its citizens (0.34–197 ng/kg depending on the year and region of the country), which is much less than other undeveloped countries [71]. The European Union (EU) has some of the world's most stringent standards for mycotoxins in food and feed. Compared with the rest of the world, the European Union (EU) has the most extensive and detailed AFB1 presence in various foods and feeds provisions. It has been indicated that in many European countries the presence of AFM1 in milk and milk products was in lower range than the Asian and African countries [72, 73].

#### **6. Summary and future direction**

AFB1 is a kind of I-type chemical carcinogenic mycotoxin mainly produced by both *A. flavus* and *A. parasiticus* and is known to contaminate most of the world's food supply. AFB1 is the most potent of these compounds and has been well

characterized to lead to the development of hepatocellular carcinoma in humans and animals. The contamination of the food chain by AFB1 has a huge impact on human health and economic damage worldwide. The prevention and detoxification strategies of AFB1 have always been the goal of research. Although physical and chemical treatment is currently the main detoxification method, it is easy to lead to the loss of food nutrition. Biotherapeutics is a relatively new detoxification method. Natural plant extracts and plant essential oils are simple to produce, biosafe, and provide an excellent source of toxin detoxification. Studies have shown that individuals' susceptibility, such as genetic polymorphisms in DNA repair genes and/or metabolic genes, play a huge role in the different detoxification and the repair of DNA damage caused by AFB1. Thus, the biofunction supplementary methods which base on this kind of genetic difference may be not only regarded as potential new detoxification methods but served as potential biological markers for predicting the occurrence of such liver diseases as liver damage, liver cirrhosis, and hepatocellular carcinogenesis.
