Aflatoxin in Chinese Commodities: Comparison
View Latest Version
Please note this is a comparison between Version 3 by Lindsay Dong and Version 2 by Lindsay Dong.

Aflatoxins (AFs) are secondary metabolites that represent serious threats to human and animal health. They are mainly produced by strains of the saprophytic fungus Aspergillus flavus, which are abundantly distributed across agricultural commodities. 

  • aflatoxins
  • Aspergillus flavus
  • occurrence
  • atoxigenic strains
  • biocontrol
  • China
  • hepatocellular carcinoma

1. Introduction

Aflatoxins (AFs) are secondary metabolites produced by members of three distinctive sections of the genus Aspergillus: section Flavi, section Ochraceorosei, and section Nidulantes [1]. Members of section Flavi are the most common and widespread producers of AFs. The most commonly known AF producing Aspergillus fungi are A. flavus and A. parasiticus. A. parasiticus appears to be more adapted to a soil environment, being prominent in peanuts, whereas A. flavus seems adapted to the aerial and foliar environment, being dominant in corn, cottonseed, and tree nuts. Thus, it is known to be the most frequently encountered producer of AFs in agricultural products because of its widespread distribution [2][3].
Plant debris, decaying wood, animal silage, dead insects, and animal carcasses are the main organic nutrient sources of A. flavus as this fungus is saprophytic in nature [4]. Although it occurs predominantly in aerial and foliar environments [5], it can even reside on human organs. For example, recent studies reported its presence in tracheal aspirates of patients infected with COVID-19 [6][7].
Aspergillus fungi can grow and proliferate almost everywhere in the world under variable climatic conditions that range from arid to tropical moist to temperate [8][9]. A. flavus requires temperatures ranging from 25 °C to 33 °C and water activity of >0.98 for active growth [10]. However, it can still grow at temperatures between 30 °C and 40 °C [11]. Thus, it occurs in all major cereal, peanut, tree nut, and cotton seed growing areas that experience high temperatures [5].
Aspergillus species produce different types of AFs, including the potent parent toxins AFB1, AFB2, AFG1, and AFG2 under natural conditions. Moreover, they generate other metabolites (AFB2a, AFG2a, AFGM1, AGM2, AFM1, aflatoxicol (R0), parasiticol (B3), and aspertoxin) [12]. Crop soils are the primary source of A. flavus, which means that important food crops can be invaded in the field and subsequent AF contamination can occur when the plants are under stress due to factors such as high soil and/or air temperature, high relative humidity, drought, or insect attacks [13][14]. AFs are generally carcinogenic [15][16], can suppress immunity [17][18], and can lead to growth impairment in children [19][20] and AFB1 is the most potent and frequently occurring AF [21]. A. flavus strains are also known to produce cyclopiazonic acid (CPA) [22], which is an indole tetramic acid that was originally discovered in peanuts as a fungal metabolite [23]. AFs and CPA commonly occur as co-contaminants and result in substantial economic losses [24][25].
Asia and Africa are the continents most affected by AF contamination. China is among the countries with a high prevalence of AFs in different agricultural products targeted for both domestic consumption and export. Studies have reported higher levels of AF contamination in crops from the southern part of China (such as Guangdong Province) compared with other regions [26][27].

2. Reports of AF Distribution in Different Commodities in China

Mycotoxin contamination is a prevailing problem in China, and it is complicated by China’s export of several agricultural products to the EU and the USA. Several studies have reported the presence of AFs in agricultural products such as cereals, peanuts, spices, milk, and animal feeds that originate from China. Several Chinese medicines have also been found to contain mycotoxigenic fungi as well as their toxins. AF contamination reported in different commodities from China from 2001 to 2020 is summarized in the tables below.

2.1. Cereals Crops

Cereals, mainly, maize, sorghum, wheat, and rice, are the most AF-vulnerable crops. A number of authors in different countries, mainly Africa and Asia, have reported AF contamination of these crops. Table 1 lists AF contamination reported in different cereal and cereal-based food products. The main food items reported to contain AFs were maize, wheat, oats, and rice and their processed products, which were collected from almost all parts of the country. The majority of the food samples tested positive for AFs. The prevalence and incidence of AF contamination are generally higher in maize.
Table 1. Aflatoxin contamination in cereal and cereal-based foods reported in China.
Province Crops Origin Period Test
Table 4. Aflatoxin contamination of animal feeds, and dairy products reported in China.
ProvinceDetection Limit (µg/kg) Mycotoxin Total Samples Incidences (%) Range of Positive Samples/Maximum Value (µg/kg) Mean ± SEM of Positive Samples/Mean (μg/kg) Level of Contamination above Chinese Regulatory Limit (%) (µg/kg) References
Table 2 lists a variety of AF-contaminated commodities, such as peanuts, walnuts, pine nuts, peanut butter, sesame paste, peanut oil, vegetable oil, sunflower oil, fish oil, and maize oil, that were collected from every part of China.
Table 2. Aflatoxin contamination in peanut, pine nut, walnut, other oil seeds and oil reported in China.
Province Crops Origin of Sample Period Analytical Method Detection Limit (µg/kg) Mycotoxin Total Samples Incidences (%) Range of Positive Samples/Maximum Value (µg/kg) Mean ± SEM of Positive Samples/Mean (μg/kg) Level Contamination above Chinese Regulatory Limit (%) References
Product Year Origin of the Sample Analytical Method Mycotoxin Detection Limit (µg/kg) Total Samples (n) Incidences (%) Range of Positive Samples/Maximum Value (µg/kg) Mean ± SEM of Positive Samples/Mean (μg/kg) Level Contamination above Chinese Regulatory Limit (%) (µg/kg or L) References
Liaoning Twelve provinces, including Liaoning, Shandong, Henan, Hebei, Jiangsu, Anhui, Jiangxi, Hubei, Hunan, Guangdong, Guangxi, and FujianMaize
Ten provincesFarmer stores

(Heilongjiang,

Inner Mongolia Beijing, Tianjin Ningxia,

2003 Hebei, Shanxi,

Shandong, North

Shanghai,

HPLC   AFs 73 Guangdong, South)Peanut with pod From farm Dairy cow feeds2011/201297 HPLC 3:1 for LOD AFB1 1040- 0.99 All < 20 25 0.01–720[28]
2.13 1% beyond Chinese regulation (20) and 3.7% above EU regulation (2) [39 2013 Dairy farms HPLC] AFB1   200 Whole grain rice
Liaoning16 100 - 3.87
Peanut From farm and storage 2015 HPLC 0.2 for AFB1; 0.05 for AFB2; 0.2 for AFG1; 0.05 for AFG2
AFB2
15
0.2–1.2
1.9 ± 0.02
1.1–35.0
6.9
4.0
[
32
]

2.3. Chinese Herbal Medicines (CHMs), Spices, Tea, Fruits, and Vegetables

In China, the maximum limits in herbs are 5 µg/kg and 10 μg/kg, respectively [43]. CHMs that have maximum limits for AFs in China are as follows: Jujubae Fructus, Hirudo, Pheretima, Myristicae Semen, Scorpio, Cassiae Semen, Hordei Fructus Germinatus, Polygalae Radix, Citri Reticulatae Pericarpium, Qutisqualis Fructus, Platycladi Semen, Sterculiae Lychnophorae Semen, Nelumbinis Semen, Persicae Semen, Scolopendra, Arecae Semen, Ziziphi Spinosae Semen, Bombyx Batryticatus, and Coicis Semen [43]. EU countries have also established stringent standards, such as commission regulation (EC) No. 165/2010, which sets the maximum limits of AFB1 for dried fruits and spices in the range of 2 to 5 μg/kg and total AFs between 4 and 10 μg/kg. Table 3 summarizes updated data for AF contamination in herbal medicines, spices, fruits, and vegetables in China.
Table 3. Aflatoxin contamination in Chinese herbal medicine, spices, tea, fruits and vegetables reported in China.
Province Product Origin of the Sample Study Year Analytical Method Mycotoxin Detection Limit (µg/kg) Total Samples (n) Incidences (%) Range of Positive Samples/Maximum Value (µg/kg) Mean ± SEM of Positive Samples/Mean (μg/kg) Level Contamination above Chinese Regulatory Limit (%) References
Eleven districts of Guangzhou Tea Household supply retail shops 2019/2020HPLC AFB1 0.1 128 17.9 0.25~4.0 0.36 ± 0.62   [36] 42 0.05–3.53 0.31 <10 [52]
AFB1 408 3.19 0.15–116.64 0.43 ± 6.23 -
Anhui, Fujian, Gansu, Guangdong, Guizhou, Hubei, Shanxi, Xinjiang, Yunnan, Zhejiang Traditional Chinese medicines (TCM)[ Herbal market 2019/202026 HPLC] AFB1 0.012–1.3 48 70.8 0.12–3.05   All < 5 [44]
AFB2   200 36 0.03–0.84 0.14 Brown rice 37 97 -
AFB2 3.680.88
- 0.05–27.36 0.11 ± 1.50
AFB2 0.43–0.5   AFB1 limit 2–10, AF’s ; 4–20 (Chinese AFB1 ≤ 5 ; AFs ≤ 10) Heilongjiang Rice Farmer stores, granaries, and markets 2009–2011
AFG1DLLME

HPLC   AFs 0.2562
AFB1 + AFB2   200 24.5 0.05–3.53 0.34 - 69 0.033–0.17 0.062 ± 0.042 All < 20 [29]
3.61 0.01 ± 0.18
AFG1 ND–0.85  
Milk Dairy farms ELISA AFM1 0.005 200 32.5% 5.2–59.6 ng/L 0.0153 <0.5 Liaoning 30 96.7 ND ND
AFG2 0.74 0.27–1.15 0.00 ± 0.06
Beijing Feed and feedstuffs 2012 Animal farms HPLC AFB1 - 22 50 59 6.0 <Chinese limit [53]
AFB2 9.1 12 15.60
AFG2 0.87–2.11 Jilin 59 40 0.030–0.98 0.12 ± 0.25
  Total AF 4.90 0.05–144.00 0.55 ± 7.80
China TCM Regulated enterprises 2011 0.6UHPLC/MS/MS AF’s LOD; 0.01–1.56 60 40 0.2–19.5     [45][46] Guangdong 138 53 0.19–4.1 0.44 ± 0.90
Henan AFB1 1190
AFG119.00 4.50.06–483.00 Guangxi 67 81 0.032–21 1.3 ± 3.7
7.57 ± 41.12
AFB1 1.2–9.8 0.5 0.0 AFB2 11.68 0.01–61.50 0.82 ± 4.67
AFG2 9.1 0.5 0.0 Hainan 14 93 0.032–0.71
AFG110.23 ± 0.32
1.18 0.33–460.00 0.81 ± 15.23 Heilongjiang LOQ = 0.009 AFB1 62 69.3 0.033–0.14 0.058 ± 0.034
Liaoning
AFB2 0.2–7.1 30 97 <LOQ <LOQ
Jilin 59 39 0.030–0.90 0.11 ± 0.23
Guangdong 138
AFG2 4.03 0.05–104.00 0.23 ± 3.3373 0.030–3.7 0.41 ± 0.81
Guangxi 67 53 0.032–20 1.2 ± 3.4
AFG1 0.6–2.5 15.56 ± 86.73
31 provinces Yoghurt 2013 Retail store and supermarkets ELISA AFM1 0.05 μg/kg 178 4.49 - 27.10 <0.5 [54 AFG2 0.2–4.8
Chongqing China TCM Local markets and

drug stores		 15.56 ± 86.73
2015 UPLC-MS/MS AF’s LOD; 0.008–0.022 22 63 0.2–7.5   18.2 exceeded the maximum limit set by EU (4) [47 AFB2 13.19 2.34 ± 13.40 2.34 ± 13.40 Hainan
AFG1 0.22 0.07 ± 1.57 0.07 ± 1.57
]
AFB1 0.2–4.8 14
AFB2 0.1–2.3
AFG1 0.1–0.8 93 0.032–0.66 0.21 ± 0.30
AFG2 5.27
]
Milk 0.005 μg/kg 233 48.07 - 21.49 <0.5
Tangshan region of China Milk 2012–2014 Milk stations HPLC-MS/MS AFM1   530 52.8% 10–200 ng/L 73.0 ng/L <0.5 [55]
China Feed   Company and livestock farms Eu-Nano-TRFIA Total AFs 0.16 μg/kg 397 78.3% 0.50–145.30 μg/kg     [56]
Northern China Raw milk 2019/2020 Shops, distributors, farms ELISA AFM1 - 84   10–430 ng/L 110 ng/kg 34.5% exceeds EU limits [57]
Commercial milk AFM1 69     AFG2 0.1–0.20.22 ± 1.82 0.22 ± 1.82
Total mixed rations (TMR) HPLC AFB1 Heilongjiang
0.03 μg/kg LOQ = 0.006 AFB2 62 14.5 0.022 0.022
22 Total AF 15.60 18.19 ± 100.38 18.19 ± 100.38
Zhejiang TCM Regulated enterprises 2009/2010 (UHPLC–MS/MS AFB1 LOD; 0.01–1.56 30 68.8 Liaoning 30 6.6 <LOQ <LOQ
Guangdong AFB1 441 11.56 0.22–341.41 4.73 ± 29.84 Jilin 59 6.5 0.086 0.086
Guangdong 138 13 0.020–0.47 0.11 ± 0.15
Guangxi 67 37.3 0.029–1.6 0.19 ± 0.36
Hainan 14 14.3 0.051 0.051
Shandong Province (Huantai County) Maize Individual households 2010 ELISA 0.1 AFB1 31 100 0.4–2.2     [30]
Rice 9 100 0.1–1.2
Wheat flour
Total AF 19.00 0.06–1023.2 9.43 ± 54.989 100 0.3–0.9
Jiangsu Province (Huaian City) Maize 43 100 1.2–136.8
Rice 10 100 0.2–0.7
Wheat flour 7
100 0.1–0.3
AFG1 ND ND ND
AFG2 2.3 1.1–1.6 1.3 ± 0.02
  30–370 ng/L- 1.40   [48]
4.16 μg/kg AFB2 50.0 1.27 AFB2 11.79 0.05–30.38 0.51 ± 2.96 Guangxi Zhuang Autonomous (Fusui County) Maize
AFG1 43.8 0.50 AFG1 0.91 0.50–11.50 0.04 ± 0.57 34
AFG2 43.8 0.94 AFG2 3.17 0.21–5.74
AFM10.06 ± 0.41
6.6 0.7 Total AF   14.29 0.06–373.69
Beijing5.34 ± 32.90
Ginger Local markets 2013/2014 100 1.0–50.0
Rice 10 100 0.3–1.4
Wheat flour - - -
Sichuan AFB1 UHPLC-FLR AFB1 0.005–0.2 30 5/30 0.3–1.38 0.073   [49] Eight regions (Chongqing, Fujian, Guangdong, Guangxi, Hubei, Jiangsu, Shanghai, Zhejiang) Peanut Local food markets 2007 HPLC - Total AF 65 15 0.03–28.39   Average 27.44 [31
AFB2]
30 ND -   Walnut 48 31 0.02–1.20
AFG1 30 ND -   Pine Nut 12 2 0.19–0.25
AFG2   30 ND -   Peanut AFB1 65 9 Eight regions (Chongqing, Fujian, Guangdong, Guangxi, Hubei, Jiangsu, Shanghai, Zhejiang)
Hebei province and Guangxi provinces0.15–22.39
Chinese yam, American ginseng, Ginseng, Notoginseng, Astragalus, Polygala, Bupleurum, Liquorice Markets 2013 UPLC-MS/MS AFB1 LOD ≤ 0.05 and LOQ ≤ 0.1 48 35.4 ND-13.3   14.58 exceed 5 [50] Walnut 48 21
AFB20.14–0.32
2 ND-8.2     Pine Nut 12 2 0.19–0.23
AFs 37.5 ND-21.5   8.33 exceed 10 Peanut AFB2 65 5 0.03–6.00
Shanghai Pistachios Markets 2014–2015 LC-MS/MS AFB1 0.03 25 4 ND-0.8 0.8 - [51] Walnut 48 12 0.02–0.70
AFB2 0.2 0 ND ND Pine Nut 12 1 0.02 Maize Local food markets 2007 HPLC 0.012 ;B1
AFG1 0.2 0 ND ND

0.008; B2;

0.036;G1		 PeanutAFs 74 52 0.02–1098.36  [31]
455 AFG1  65 4 0.42–11.73
AFG2 0.3 0 ND ND AFB1 74 46 0.14–970.32 23.91 above 20
Walnut 48 8 0.36–0.83
31.8% exceeds EU limits
Central China Feed 2016/2017   HPLC AFB1 0.03 μg/kg 174 35.1%     2.3% (30) [58]
UHT milk ELISA AFM1 0.005 μg/kg 111 73.6% - 100.0 ng/L All below 0.5
Pasteurized milk ELISA AFM1 131 -
China (Beijing and Shanghai) UHT milk 2010 super-

markets		 ELISA AFM1 - 153 54.9% 0.006–0.160 mg/L - All below 0.5 [59] Dried longans AFB1 0.1 28 0 ND ND AFB2 74 41 0.02–128.04  
Pasteurized milk - 26 96.2% 0.023–0.154 mg/L - Pine Nut 12 0
AFB2-
0.1 3.6 ND-0.2 0.2 AFG1 74 9 0.36–4.76
Shandong Province (Huantai County), Jiangsu Province (Huaian City), and Guangxi Zhuang Autonomous (Fusui County) Plant oil Individual households 2010/2011 ELISA 0.1 AFB1 39 100 0.5–114.4   Median level is 52.3 beyond the Chinese standard 10 Rice AFs 84 23 0.15–3.88
[ AFB1 84 16 0.15–3.22
Guangxi; Zhuqing Village, Fusui,
AFG1 0.230]
0 ND ND Peanut 17 100 0.1–0.7    
AFG2 0.3 0 ND ND Hebei Province Shijiazhuang Edible oil (peanut, blended,

soybean, maize,

sunflower, fish oil)		 Local markets 2011 LC–MS/MS
Raisins  AFB1 40 32.5 0.14–2.72     [40] AFB1 0.1 32 0 ND ND AFB2 84 3 0.06–0.24
AFB2 0.3
AFB2 12.5 0.15–0.36   0 ND ND AFG1 84 7 0.36–1.59
AFG1 7.5 0.01–0.02  
AFG1 0.3 0 ND ND Yangtze Delta region (Hangzhou, Ningbo, Shanghai, Suzhou and Wuxi cities) Rice, wheat, maize, oats, soya bean Supermarkets and wholesale markets
AFG22010 0.3IAC-fluorometer 1 AFs 76 14.5 0 ND ND1.1–35.0 6.9 4.0 beyond Chinese (20) and 6.6 beyond EU(4) [32]
Baoding AFB1 18 22.2 0.16–1.88   1 AFB1 76 14.5 1.0–32.2 6.6 4 beyond Chinese limit (20) and 9.2 beyond EU limit (2)
AFB2
Dried dates5.56 AFB10–0.18 0.1  40 0 ND ND Hangzhou Cereal based infant food Supermarkets 2012 UPLC-MS/MS
AFB2 0.1 0 ND ND
20.3% of UHT milk samples and 65.4% of pasteurized milk samples exceed the EU limit 0.001 AFB1 AFG1 0.3 0 ND ND
AFG2 0.3 0 ND ND
21 provinces, autonomous regions and municipalities Dried jujube Local markets and supermarkets 2018 UPLC-MS/MS AFB1 LOD; 0.05–1.00

and LOQ; 0.10–5.00		 35 0 ND ND   [42]
AFB2 0 ND ND
AFG1 8.6 0.2–0.6 0.4 ± 0.03
AFG2

43. Health Impacts of AFs in China

Human dietary AF exposure can result in either chronic or acute health risks depending on the extent of exposure. In one remarkable case, 125 Kenyans died between 2004 and 2006 due to acute liver failure after consumption of homegrown maize containing high levels (up to 4400 ppb) of AFs [60][61][62]. Stunted growth, immunosuppressive effects, and cancer are also chronic health complications of AF consumption [17][18][62]. Among the AFs, AFB1 is known to cause liver cancer and, in synergism with the hepatitis B virus (HBV), to increase the possibility of developing chronic liver disease (CLD) or HCC [63][64]. AF parent molecules (like AFB1) are relatively harmless, but the electrophilic intermediates AFBO (B1-8,9-epoxide) that are generated at the predominant AF metabolization site are mutagenic and carcinogenic [65][66]. The major human cytochrome p450 enzymes are responsible for converting AFB1 into two reactive 8,9-epoxide stereoisomers (exo and endo) [62]. Exo-isomers are more toxic and cause the AFB1 to exhibit genotoxic characteristics [67]. The exo-8,9-epoxide has a high binding affinity for DNA, forming AF-DNA adducts, which primarily exist as 8,9-dihydroxy-8-(N7) guanyl-9-hydroxy-AFB1 (AFB1-N7-Gua) adducts. These adducts are primarily responsible for the genotoxic, mutagenic, and carcinogenic properties of AFB1 [21]. Human dietary AF exposure is usually measured using several biomarkers. Biomarkers help to assess AF exposure to more accurately reflect individual intake of AFs, and they are measured in urine or blood serum. The AF albumin adduct (AF-alb) in serum is a valuable biomarker for CLD and HCC due to long-term high AF exposure [68][69][70]. The most commonly used biomarkers are the urinary AFB1-N7-Gua adduct, which is a product of DNA damage, and the metabolites of AFM1 in urine or milk (AFP1, AFB1, AFQ1, AFP1, AFB-N-acetyl-L-cysteine (AFB1-mercapturic acid)) [37][71][72]. In China, studies of AFs and HCC risks have been conducted for more than three decades, with the earliest report dating back to 1989 [73]. That study confirmed the roles of the HBV virus and AFB1 in the rate of primary hepatocellular carcinoma (PHC) in southern Guangxi, China, which was the most PHC-prevalent region in the world. A number of other researchers have reported elevated AF exposure and higher incidences of HCC in different cities/counties of China in the provinces/municipalities of Jiangsu, Guangxi, Guangdong, Shanghai, and Taiwan [37][31][74][75], as regions in the southern parts of China are prone to AF contamination because their humid and warm climate is suitable for the growth and proliferation aflatoxigenic fungi [26][27]. Guangxi Province is a well-studied region of China due to its high rate of HCC morbidity, mortality, and AF exposure. Wang et al. (2001) [37] conducted a study in Zhuqing Village, Fusui County, Gangxi, aimed at determining the correlation between AF exposure, chronic HBV, and HCC cases. In this study, AFB1 contents of the major food items in the area were evaluated, and it was detected in 76.7% of maize (range 0.4–128.1 ppb), 66.7% of cooking oil (range 0.1–52.5 ppb), and 23.3% of rice (range 0.3–2.0 ppb). The mean levels of serum AFB1-albumin adducts in 29 identified HCC groups were >1.2 pmol/mg of albumin at both the beginning and end of the study period, and urinary AFB1 metabolites were detected in 88.9% of samples (range 0.9–3569.7 ng/24 h urine). The study also concluded that HCC accounted for 64% of the total cancer cases in the area. Another comparative epidemiological study was conducted in China to identify the potential factors modulating AF exposure among three locations: Fusui County and Nanning City in Guangxi Province and Chengdu City in Sichuan Province [74]. These three locations had HCC rates of 92–97, 32–47, and 21 per 100,000 people, respectively. Residents were screened for AF-alb adducts and human papilloma virus (HPV) infection. Higher numbers of HPV-positive people (47%) were found among Fusui residents compared to Nanning (15%) and Chengdu (22%) residents. This suggests a co-effect of HPV infection and AFB1 exposure in the high risk of HCC in the Fusui region. Taiwan is another province of China that has a high rate of dietary AF exposure and HCC prevalence. Wan et al. (1996) [75] published one of the earliest reports about AF-related HCC cases in Taiwan. They surveyed seven townships, including those with the highest HCC incidence. Detectable concentrations of the AF-alb adduct and urinary AF metabolites were highly correlated with HCC in 56 cases, and the authors concluded that AF exposure was enhancing the risk of HCC associated with HBV. In a similar study designed to elucidate the importance of AF exposure in the etiology of HCC, researchers conducted a community-based cohort epidemiological study in the Taiwan Penghu Islets, where the HCC mortality rate was highest [76]. In this study AF exposure was evaluated in inhabitants (6487) via regular follow-up. AFB1-albumin adducts were detected in 60% of HBsAg-positive HCC cases, and the authors concluded that a higher risk of developing HCC was attributable to both a heavy exposure to AFs and high HPV incidence. During the last 30 years, changes in China have led to a significant drop in AF-associated HCC prevalence and HCC mortality. This decrease might be due to socioeconomic changes and changes in the consumption pattern of maize, which dramatically decreased among Chinese families from 1980 to 2000 [77]. Additionally, after adoption of the national children’s HBV vaccination program (1980–1990), the prevalence of HCC has dropped significantly. Evidence for this decline comes from a recent cancer registration report showing about an 83% reduction of HCC mortality in Qidong, which was one of the regions with the highest prevalence [78]. The reduction of HCC incidence is also evident in results of a longitudinal (28 year) study that utilized follow-ups of etiological interventions among 1.1 million inhabitants of this area [78]. In this study there was a controlled neonatal HBV vaccination program (1980–1990) and economic reforms beginning in 1980 that were aimed at changing the consumption pattern from maize to rice and wheat. Compared with 1980–1983, the age-specific liver cancer incidence rates in 2005–2008 significantly decreased by 14-fold (ages 20–24), 9-fold (ages 25–29), and 4-fold (ages 30–34). The reduction among 20–24 year-olds might reflect the combined effects of reduced AF exposure and neonatal HBV vaccination, whereas the decreased incidence in the age groups of >25 years may be attributable mainly to a rapid reduction of AF exposure.

54. AF Standards in China and Recent Updates

AFs are the most regulated mycotoxins due to their toxicities and health risks, particularly carcinogenicity. Over 100 countries have defined maximum limits for AFs [79][80]. For cereals and nuts, most maximum limits range between 10 and 20 µg/kg, although the EU sets the lowest limit at 4 µg/kg [81]. Most countries set the maximum limits of AFM1 at either 0.05 µg/kg (EU) or 0.5 µg/kg. Currently, the Chinese government also has regulations on the maximum limits of AFs allowed in different foodstuffs. In maize, peanuts, peanut oil, nuts (walnuts, almonds), and dried fruit, the maximum limit of AFB1 is 20 μg/kg, whereas the limit in rice and oils (sesame, rapeseed, soybean, sunflower, flax, maize germ, bran, cottonseed) is 10 μg/kg. In milk and milk products (fresh raw milk, whole milk powder, evaporated milk, sweet condensed milk) and butter the AFM1 limit is 0.5 μg/kg, excluding liquid infant formula [82]. The establishment of mycotoxin legislation and regulations is dynamic both in terms of addressing newly identified toxins and maintaining rigorous limits. For instance, the EU has made the maximum tolerable limits more stringent over time [81][83]. It has been two decades since the Chinese government first imposed national food safety standards on maximum levels of mycotoxins in foods. Mycotoxin food standards were established in China in 2003 for the first time (GB 9676-2003) and considered toxins such as AFB1, AFM1, DON, and patulin, and they were renewed in 2005 (GB2761-2005). In 2011, GB2761-2011 added maximum limits of OTA and ZEN and considered baby foods and other special food groups [84]. In 2017, the Chinese maximum levels of mycotoxins in foods were updated, with a special emphasis on vulnerable groups of society (GB2761-2017). In this version, the maximum limit of AFB1 in infant formula and supplementary foods for infants, young children, and pregnant and lactating woman was set at 0.5 µg/kg. In 2019, GB 2761 lowered the maximum AFM1 limit from 0.5 to 0.2 µg/kg in liquid infant formula, which includes raw milk, pasteurized dairy, sterilized dairy, modified dairy, and fermented dairy. It also added a maximum limit for fumonisins (200 μg/kg) in cereal-based (maize or maize flour) auxiliary foods for infants [85]. Other common AFs (e.g., B2, G1, and G2) are being detected in different foods in China and are known to be carcinogenic, but they and total AFs are not yet regulated.

75. Distribution and Genetic Characteristics of Aspergillus Species in China

The most important fungi responsible for AF contamination in China are the three members of Aspergillus section Flavi: A. flavus, A. parasiticus, and A. nomius [86]. Hence, understanding the distribution and mycotoxin (AFs and CPA) production capacities and the genetic makeup of these fungi is crucial for broader AF management and for designing preharvest and postharvest mitigation strategies. Interest in the distribution of A. flavus across different agro-ecologies, geographical locations, crops, and crop soils has also been increasing in China, due to the possibility of using isolates of atoxigenic A. flavus strains to reduce AF contamination. Thus, several reports describing the nature and distribution of Aspergillus section Flavi in China have been published, and they are summarized in Table 5.
Table 5. Distribution of Aspergillus flavus reported by different authors in China.
Location Product Number of Samples Source Sampling Season Incidences of Fungi, or Aspergillus spp. or Aspergillus Section Flavi Incidences of A. flavus Species Toxin Production of A. flavus Strains Nature Biosynthetic Genes Morphological Nature Reference
Liaoning Province

(Northeast)		 Maize 120 Household stored (1–3 years) 2003 55.8% (Aspergillus section Flavi) 98.5% - - 64%-L

36%-S		 [27]
Guangxi

province		 Maize 89   2016/2017 195 (Aspergillus section Flavi) 98.5% 86.6% (30) were aflatoxin and CPA positive - Fluorescence and pink color observed in carbon added PDA [87]
19 provinces, 1 autonomous region and 1 municipality Peanut, maize, rice - - 2013/2014 724 A.flavus species isolated >95% 32% (229) atoxigenic 10.4% atoxigenic strains found to have lost aflR, fas-1 and aflJ genes 51% S-type (229)

34% L- type (229)15% NS (229)		 [88]
2.9
14 provinces Peanut pod 1106   2013 265 Aspergillus spp.
0.4
0.4 ± 0.06
262 (98.9%) 18.8% A.flavus atoxigenic 38.0% atoxigenic strains lost nor-1, ver-1, aflR, omtA genes - [89] - Field - - 56 A.flavus 35 atoxigenic 11 A. flavus isolates had 5 deletion patterns for 12 genes 21 atoxigenic strains were either L- or S-type [92]
30
Tangshan
6.6
AFG1
0
-
 
0.016–0.024
 
 
[
33
]
0.001
AFB2 0 ND
AFB1 18 27.8 0.15–0.45   0.002 AFG1 0 ND
AFB2 0 0.006 AFG2 0 ND
-  
AFG1 0 -   0.008
Beijing, Shanghai, Changchun, Chengdu, Shijiazhuang, and ZhengzhouAFM1 0 ND
Peanut butter Retail markets 2007 LC 1 AFT 50 82 0.77–70.64 8.51 39% for total AFs set by EU (4)

37% AFB1 set by EU (2)

and 2% AFB1 exceed the Chinese regulations (20);		 [41] 0.004 AFM2 0 ND
0.15 AFB1 0.39–68.51 6.12

6		 Chongzuo County and Guilin suburbs, Guangxi autonomous region Maize Individual households 1998 HPLC 1 AFB1 40 45 9–2496 460 ± 732 76% AFB1positive samples above Chinese limit (20) [34]
AFB2 0–5.52 0.67 2.5 AFB2 35 11–320 82 ± 102
AFG1 0–21.22 Raisins2 AFB1 30 10 AFG1 22.5 12–21 15 ± 3
0 ND ND AFG2 0–6.36 0.4 10
AFB2 0 ND ND AFG2 0 ND ND
AFG1 0 ND ND Taiwan Coffee, red yeast rice and maize Local stores 2013 ELISA
Sesame paste 1 AFT 50 37 0.54–56.89 6.75 24% beyond the limits total AFs of EU (4)

19% and 32% of sesame AFB1 exceed Chinese (5) and European Union (EU) (2)		 1–2
0.15 AFB1 0.39–20.45AFB1 36 55.5 1.7–234.0 4.31  30% are beyond the Taiwan limit (15) [35]
AFG2 20 Eleven districts of Guangzhou Rice and rice products Household supply retail shops 2015–2017 HPLC 0.1 AFB1 4901.42 0.28–1.00 0.13 ± 0.001   [36]
0.5–1.4 0.9 ± 0.02 AFB2 0–4.92 0.63 Wheat and wheat products 436
Dried figs AFB1 1.4 0.28–1.46 0.13 ± 0.001
20 AFG1 0–26.28 1.44 339 0.9 1.50–6.30 0.17 ± 0.001
AFG2 0–5.75 0.37 Maize and maize products
15 1.8–384.1 129.5 ± 0.68
AFB2 5 2.5 2.5 ± 0.21
AFG1 15 0.4–17.8 5.9 ± 0.33 Eleven districts of Guangzhou Nuts Household supply retail shops 2015–2017 HPLC 0.1 AFB1 96 3.1 0.62–1.37 0.14 ± 0.001   [36] Guangxi ; Zhuqing Village, Fusui, Maize Households 1999
AFG2 15
2015 257 Aspergillus spp. 254 (98.8%)  
12 provinces Rice - - - - 127 A.flavus 47(37%) toxigenic - - [90] 0.6–1.2
Provinces Liaoning Peanut-cropped soils - Field 2013 343 fungi isolated 9 323 76 Atoxigenic [91 ELISA - AFB1 30 76.7 0.4–128.1 23.7 ± 6.6 30% beyond (20) [37]
] 97% of atoxigenic strains lost one of the aflT, nor-1, aflR, hypB genes  
Shandong 73  
Hubei 125   0.9 ± 0.05 Vegetable oil 365
Guangdong 116   38.9 Dried longans AFB10.26–283.0 156.32 ± 25.99 ND ND ND Rice 30 23.3 0.3–2.0 1.1 ± 0.3
Commercial vegetable oil 
269
AFB2 6.7 0.7
Different provinces of China Peanut cropped soil 25 0.35–7.30 0.67 ± 1.81 0.7 ± 0.01 Shigatze Prefecture of Tibet Autonomous Region Barley Farms 1998 CD-ELISA   AFs 25 4 0.0 - 0.04  
Home-made peanut oil 96[ 75.538]

2.2. Peanuts, Pine Nuts, Nuts, Oils, and Other Oil Products

AFG1
0.26–283.0
ND
38.74 ± 47.45
The mean Is 7 times larger that the Chinese maximum limit (5)
ND
ND
21 provinces, autonomous regions and municipalities
Nuts
Local markets and supermarkets
2018
UPLC
LOD; 0.05–1.00;


LOQ; 0.10–5.00
AFB1
133
3.8
1.3–40.7
9.3 ± 0.28
AFG2
 
[
42
]
40
0.1–2.9
1.5 ± 0.07
Peanut
Households
2013 ELISA - AFB1 30 66.7 0.1–52.5 7.8 ± 3.2   [37]
Yangtze Delta region (Hangzhou, Ningbo, Shanghai, Suzhou and Wuxi cities) Peanut, soya bean, and oil. Supermarkets and wholesale markets   IAC-fluorometer 1 AFs 76 14.5

2.4. Animal Feed and Dairy Products

Table 4 lists AFs that were detected in feeds and dairy products collected from different parts of China and shows that the prevalence of AFs in both feedstuffs and dairy products is high. However, the levels of most of these toxins are far below China’s maximum limits for feeds and dairy products.

86. Atoxigenic A. flavus as AF Biocontrol Agents

Recent developments in the field of mycotoxin prevention have led to renewed interest in seeking effective, feasible, and environmentally friendly control strategies. Biological methods, which basically utilize naturally occurring microorganisms or their enzymes or extracts, have been confirmed to have fewer food safety problems and environmental impacts compared to chemical methods. Biological control methods are also promising because they are very specific for specific toxins. Over the last three decades, numerous investigations have been conducted to explore potential biological control agents (e.g., fungi, bacteria, enzymes, and proteins) that can reduce mycotoxin levels either by inhibiting fungal growth and/or proliferation and subsequent mycotoxin production, or by degrading (transforming) them into harmless metabolic products. The application of atoxigenic A. flavus is now becoming a widely applicable biocontrol mechanism. The effect is achieved by applying naturally occurring competitive native atoxigenic strains of A. flavus to the soil [93]. Atoxigenic A. flavus strains interfere with the proliferation of indigenous toxigenic strains [13][94][95][96][97]. Atoxigenic strains that are inoculated in the soil have been shown to have a carry-over effect that may inhibit peanut contamination during storage [98], which makes the method more acceptable because it may reduce AF contamination during both preharvest and postharvest. Several countries (USA, Italy, Argentina, Nigeria, Australia, and Thailand) are either developing or already using this native biocontrol agent widely [13][94][95][96][97]. In doing so, they have achieved significant levels of AF reduction (43–98%). Several atoxigenic strains of A. flavus have been patented, registered, and commercialized. In the USA between 2004 and 2008, the atoxigenic A. flavus strains NRRL 21,882 (active component of Afla-guard®) and AF36 (NRRL 18543) were registered and used [99] widely. Strain K49 (NRRL 30797) was also patented by the USDA [100]. In order to develop sustainable AF biocontrol, the population dynamics and genetic stability of A. flavus populations in the field must be carefully examined. Due to the possibility of recombination with toxigenic strains, atoxigenic A. flavus strains could develop the ability to produce AFs [101]. Therefore, it is critical to assess the frequency of such events in agricultural environments where atoxigenic biocontrol A. flavus has been introduced [102]. Analysis of vegetative compatibility groups (VCGs) is critical, as VCGs are a strong barrier to sexual recombination [103]. Atoxigenic biocontrol isolates selected for use should belong to VCGs that contain only atoxigenic strains and have wide distributions [104], as different VCGs are clonal lineages that differ in many characteristics, including AF-producing ability [105].

97. Conclusions and Recommendations

Historically, mycotoxins, especially AFs, were the most prevalent toxins in China. The incidence of HCC cases due to AF exposure was also among the highest in China compared to other countries. Some regions of China are particularly prone to AF contamination due to the climate and geographical location. However, strong Chinese AF regulations, control measures, such as good agricultural and manufacturing practices that include preventive strategies from preharvest to postharvest, policy implementations, and national HBV vaccinations are yielding encouraging results in terms of reduced AF prevalence and exposure risks. Nonetheless, as revealed in some reports reviewed herein, the prevalence of AFs in some agricultural products is still relatively high compared to the national maximum limits. Thus, there is still a need for extensive surveys of AF contamination in food and foodstuffs as well as human biomarker monitoring in order to improve risk management.
Feasible mechanisms to reduce toxic AF levels throughout the food chain, from farm to storage and processing, are needed. The application of native atoxigenic A. flavus as a biocontrol mechanism is currently being used in different countries, as it is easy to use and environmentally friendly. Soil treatment with atoxigenic strains offers the extra advantage in the carry-over effect of reducing AF contamination that occurs during storage. According to several reports from China, several indigenous atoxigenic A. flavus can be used as biocontrol agents. However, little is known about the potential of these native strains at the experimental level or under field conditions. The few existing studies suggest that these native strains show a promising competitive ability to displace toxigenic strains and reduce AF levels [106][107][108]. Thus, there is a need for more studies to characterize and search for potential AF biocontrol strains of A. flavus and to develop formulations and application techniques for these biocontrol strains in the field. Extensive field trials must be conducted across China in areas where potential AF contamination risks are high. Finally, VCG tests should be conducted to ensure genetic stability of atoxigenic strains and to test for their recurrent efficiency.

References

  1. Frisvad, J.C.; Larsen, T.O.; De Vries, R.; Meijer, M.; Houbraken, J.; Cabañes, F.J.; Ehrlich, K.C.; Samson, R.A. Secondary metabolite profiling, growth profiles and other tools for species recognition and important Aspergillus mycotoxins. Stud. Mycol. 2007, 59, 31–37.
  2. Frisvad, J.C.; Thrane, U.; Samson, R.A.; Pitt, J.I. Important mycotoxins and the fungi which produce them. In Advances in Experimental Medicine and Biology; 2006; Volume 571, pp. 3–31. ISBN 0065-2598.
  3. Frisvad, J.C.; Hubka, V.; Ezekiel, C.N.; Nov, A.; Chen, A.J.; Arzanlou, M.; Larsen, T.O.; Sklen, F.; Mahakarnchanakul, W.; Samson, R.A.; et al. Taxonomy of Aspergillus section Flavi and their production of aflatoxins, ochratoxins and other mycotoxins. Stud. Mycol. 2019, 63, 1–63.
  4. Razzaghi-Abyaneh, M.; Shams-Ghahfarokhi, M.; Allameh, A.; Kazeroon-Shiri, A.; Ranjbar-Bahadori, S.; Mirzahoseini, H.; Rezaee, M.B. A survey on distribution of Aspergillus section Flavi in corn field soils in Iran: Population patterns based on aflatoxins, cyclopiazonic acid and sclerotia production. Mycopathologia 2006, 161, 183–192.
  5. Diener, U.L.; Sanders, J.C.T.H.; Lee, P.L.S.; Klich, M.A. Epidemiology of Aflatoxin Formation by Aspaergillus flavus. Ann. Rev. Phytopathol. 1987, 25, 249–270.
  6. Blaize, M.; Mayaux, J.; Nabet, C.; Lampros, A.; Marcelin, A.; Thellier, M.; Piarroux, R.; Demoule, A. Fatal Invasive Aspergillosis and Coronavirus Disease in an Immunocompetent Patient. Emerg. Infect. Dis. 2020, 26, 1636–1637.
  7. Lescure, F.; Bouadma, L.; Nguyen, D.; Parisey, M.; Wicky, P.; Behillil, S.; Gaymard, A. Clinical and virological data of the first cases of COVID-19 in Europe: A case series. Lancet Infect. Dis. 2020, 2, 1–10.
  8. Passone, M.A.; Resnik, S.; Etcheverry, M.G. Potential use of phenolic antioxidants on peanut to control growth and aflatoxin B1 accumulation by Aspergillus flavus and Aspergillus parasiticus. J. Sci. Food Agric. 2007, 87, 2121–2130.
  9. Kumar, V.; Basu, M.S.; Rajendran, T.P. Mycotoxin research and mycoflora in some commercially important agricultural commodities. Crop Prot. 2008, 27, 891–905.
  10. Neme, K.; Mohammed, A. Mycotoxin occurrence in grains and the role of postharvest management as a mitigation strategies. A review. Food Control 2017, 78, 412–425.
  11. Agriopoulou, S.; Stamatelopoulou, E.; Varzakas, T. Control Strategies : Prevention and Detoxification in Foods. Foods 2020, 137, 1–48.
  12. Benkerroum, N. Aflatoxins : Producing-Molds, Structure, Health Issues and Incidence in Southeast Asian and Sub-Saharan African Countries. Int. J. Environ. Res. Public Health 2020, 17, 1215.
  13. Pitt, J.I.; Manthong, C.; Siriacha, P.; Chotechaunmanirat, S.; Markwell, P.J. Studies on the biocontrol of aflatoxin in maize in Thailand. Biocontrol Sci. Technol. 2015, 25, 1070–1091.
  14. Barros, G.; Torres, A.; Chulze, S. Aspergillus flavus population isolated from soil of Argentina’s peanut-growing region. Sclerotia production and toxigenic profile. J. Sci. Food Agric. 2005, 85, 2349–2353.
  15. Liu, Y.; Wu, F. Global burden of Aflatoxin-induced hepatocellular carcinoma: A risk assessment. Environ. Health Perspect. 2010, 118, 818–824.
  16. IARC (International Agency for Research on Cancer). Evaluation of Carcinogenic Risks to Humans; Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene; Lyon, France, 2002.
  17. Mupunga, I.; Mngqawa, P.; Katerere, D.R. Peanuts, aflatoxins and undernutrition in children in Sub-Saharan Africa. Nutrients 2017, 9, 1287.
  18. Okoth, S. Improving the Evidence Base on Aflatoxin Contamination and Exposure in Africa; The Technical Centre for Agricultural and Rural Cooperation, CTA: Wageningen, The Netherlands, 2016.
  19. Gong, Y.Y.; Egal, S.; Hounsa, A.; Turner, P.C.; Hall, A.J.; Cardwell, K.F.; Wild, C.P. Determinants of aflatoxin exposure in young children from Benin and Togo, West Africa: The critical role of weaning. Int. J. Epidemiol. 2003, 32, 556–562.
  20. Gong, Y.Y.; Cardwell, K.; Hounsa, A.; Egal, S.; Turner, P.C.; Hall, A.J.; Wild, C.P. Dietary aflatoxin exposure and impaired growth in young children from Benin and Togo: Cross sectional study. BMJ 2002, 325, 20–21.
  21. Kew, M.C. A atoxins as a Cause of Hepatocellular Carcinoma. Reviews 2013, 22, 305–310.
  22. Chang, P.-K.; Ehrlich, K.C.; Fujii, I. Cyclopiazonic Acid Biosynthesis of Aspergillus flavus and Aspergillus oryzae. Toxins 2009, 1, 74–99.
  23. Holzapfel, C.W. The isolation and structure of cyclopiazonic acid a toxic metabolite of Penicillium cyclopium Westling. Tetrahedron 1968, 24, 2101–2119.
  24. Bamba, R.; Sumbali, G. Co-occurrence of aflatoxin B1 and cyclopiazonic acid in sour lime (Citrus aurantifolia Swingle) during post-harvest pathogenesis by Aspergillus flavus. Mycopathologia 2005, 159, 407–411.
  25. Astoreca, A.; Vaamonde, G.; Dalcero, A.; Marin, S.; Ramos, A. Abiotic factors and their interactions influence on the co-production of aflatoxin B1 and cyclopiazonic acid by Aspergillus flavus isolated from corn. Food Microbiol. 2014, 38, 276–283.
  26. Wu, L.X.; Ding, X.X.; Li, P.W.; Du, X.H. Aflatoxin contamination of peanuts at harvest in China from 2010 to 2013 and its relationship with climatic conditions. Food Control 2016, 60, 117–123.
  27. Gao, J.; Liu, Z.; Yu, J. Identification of Aspergillus section Flavi in maize in northeastern China. Mycopathologia 2007, 164, 91–95.
  28. Liu, Z.; Gao, J.; Yu, J. Aflatoxins in stored maize and rice grains in Liaoning Province, China. J. Stored Prod. Res. 2006, 42, 468–479.
  29. Lai, X.; Liu, R.; Ruan, C.; Zhang, H.; Liu, C. Occurrence of aflatoxins and ochratoxin A in rice samples from six provinces in China. Food Control 2015, 50, 401–404.
  30. Sun, G.; Wang, S.; Hu, X.; Su, J.; Zhang, Y.; Xie, Y.; Zhang, H.; Tang, L. Co-contamination of aflatoxin B1 and fumonisin B1 in food and human dietary exposure in three areas of China. Food Addit. Contam. Part A 2011, 28, 461–470.
  31. Wang, J.; Liu, X.-M. Contamination of aflatoxins in different kinds of foods in China. Biomed. Environ. Sci. 2007, 20, 483–487.
  32. Li, R.; Wang, X.; Zhou, T.; Yang, D.; Wang, Q.; Zhou, Y. Occurrence of four mycotoxins in cereal and oil products in Yangtze Delta region of China and their food safety risks. Food Control 2014, 35, 117–122.
  33. Taylor, P.; Jin, Q.; Liu, S.; Huang, X.; Zhu, G. Determination of Aflatoxin in Infant Cereals from Hangzhou, China. Anal. Lett. 2013, 46, 2319–2331.
  34. Li, F.; Yoshizawa, T.; Kawamura, O.; Luo, X.; Li, Y. Aflatoxins and Fumonisins in Corn from the High-Incidence Area for Human Hepatocellular Carcinoma in Guangxi, China. J. Agric. Food Chem. 2001, 2001, 4122–4126.
  35. Liu, B.; Hsu, Y.; Lu, C.; Yu, F. Detecting aflatoxin B1 in foods and feeds by using sensitive rapid enzyme-linked immunosorbent assay and gold nanoparticle immunochromatographic strip. Food Control 2013, 30, 184–189.
  36. Zhang, W.; Liu, Y.; Liang, B.; Zhang, Y.; Zhong, X.; Luo, X. Probabilistic risk assessment of dietary exposure to aflatoxin B1 in. Sci. Rep. 2020, 10, 7973.
  37. Wang, J.; Huang, T.; Su, J.; Liang, F.; Wei, Z.; Liang, Y.; Luo, H.; Kuang, S.-Y.; Qian, G.-S.; Sun, G.; et al. Hepatocellular Carcinoma and Aflatoxin Exposure in Zhuqing Village, Fusui County, People’s Republic of China. Cancer Epidemiol. Biomark. Prev. 2001, 10, 143–146.
  38. Suetens, C.; Haubruge, E. Mycotoxins in Stored Barley (Hordeum vulgare) in Tibet Autonomous Region (People’s Republic of China). Mt. Res. Dev. 2003, 23, 284–287.
  39. Ding, X.; Li, P.; Bai, Y.; Zhou, H. Aflatoxin B1 in post-harvest peanuts and dietary risk in China. Food Control 2012, 23, 143–148.
  40. Taylor, P.; Yang, L.; Liu, Y.; Miao, H.; Dong, B.; Yang, N.; Chang, F. Determination of aflatoxins in edible oil from markets in Hebei Province of China by liquid chromatography–tandem mass spectrometry. Food Addit. Contam. Part B Surveill. 2011, 4, 244–247.
  41. Li, F.-Q.; Li, Y.-W.; Wang, Y.-R.; Luo, X.-Y. Natural Occurrence of Aflatoxins in Chinese Peanut Butter and Sesame Paste. J. Agric. Food Chem. 2009, 57, 3519–3524.
  42. Yu-jiao, W.; Ji-yun, N.I.E.; Zhen, Y.A.N.; Zhi-xia, L.I.; Yang, C.; Farooq, S. Multi-mycotoxin exposure and risk assessments for Chinese consumption of nuts and dried fruits. J. Integr. Agric. 2018, 17, 1676–1690.
  43. Dan, Y.; Qian, Z.; Peng, Y.; Chen, C.; Liu, Y.; Tai, W.; Qi, J. Revision and Improvement of Criterion on Traditional Chinese Medicines in Chinese Pharmacopoeia 2015. Chinese Herb. Med. 2016, 8, 196–208.
  44. Chen, L.; Guo, W.; Zheng, Y.; Zhou, J.; Liu, T.; Chen, W.; Liang, D. Occurrence and Characterization of Fungi and Mycotoxins in Contaminated Medicinal Herbs. Toxins 2020, 12, 30.
  45. Ashiq, S.; Hussain, M.; Ahmad, B. Natural occurrence of mycotoxins in medicinal plants: A review. Fungal Genet. Biol. 2014, 66, 1–10.
  46. Han, Z.; Ren, Y.; Zhu, J.; Cai, Z.; Chen, Y.; Luan, L.; Wu, Y. Multianalysis of 35 mycotoxins in traditional Chinese medicines by ultra-high-performance liquid chromatography-tandem mass spectrometry coupled with accelerated solvent extraction. J. Agric. Food Chem. 2012, 60, 8233–8247.
  47. Zhao, S.; Zhang, D.; Tan, L.; Yu, B.; Cao, W. Analysis of aflatoxins in traditional Chinese medicines : Classification of analytical method on the basis of matrix variations. Sci. Rep. 2016, 6, 30822.
  48. Han, Z.; Zheng, Y.; Luan, L.; Cai, Z.; Ren, Y.; Wu, Y. An ultra-high-performance liquid chromatography-tandem mass spectrometry method for simultaneous determination of aflatoxins B1, B2, G1, G2, M1 and M2 in traditional Chinese medicines. Anal. Chim. Acta 2010, 664, 165–171.
  49. Wen, J.; Kong, W.; Hu, Y.; Wang, J.; Yang, M. Multi-mycotoxins analysis in ginger and related products by UHPLC-FLR detection and LC-MS/MS con fi rmation. Food Control 2014, 43, 82–87.
  50. Su, C.; Hu, Y.; Gao, D.A.N.; Luo, Y.I.; Chen, A.J.; Jiao, X.; Gao, W. Occurrence of Toxigenic Fungi and Mycotoxins on Root Herbs from Chinese Markets. J. Food Prot. 2018, 81, 754–761.
  51. Han, Z.; Dong, M.; Han, W.; Shen, Y.; Nie, D.; Shi, W.; Zhao, Z. Occurrence and exposure assessment of multiple mycotoxins in dried fruits based on liquid chromatography-tandem mass spectrometry. World Mycotoxin J. 2016, 9, 465–474.
  52. Han, R.W.; Zheng, N.; Wang, J.Q.; Zhen, Y.P. Survey of a flatoxin in dairy cow feed and raw milk in China. Food Chem. 2013, 34, 35–39.
  53. Yu, F.A.N.; Xiao-ying, L.I.; Li-hong, Z.; Ya-xiong, J.I.A.; Cheng, J.I.; Qiu-gang, M.A.; Yu, C.; Liang, W. Investigation on Contamination Situation of Aflatoxin in Detected Feeds and Feedstuffs in Beijing Area. Sci. Agric. Sin. 2012, 45, 5102–5109.
  54. Guo, Y.; Yuan, Y.; Yue, T. Aflatoxin M 1 in Milk Products in China and Dietary Risk Assessment. J. Food Prot. 2013, 76, 849–853.
  55. Guo, L.Y.; Zheng, N.; Zhang, Y.D.; Du, R.H.; Zheng, B.Q.; Wang, J.Q.; Zheng, N.; Zhang, Y.D.; Du, R.H.; Zheng, B.Q.; et al. A survey of seasonal variations of aflatoxin M1 in raw milk in Tangshan region of China during 2012–2014. Food Control 2016, 69, 30–35.
  56. Wang, D.; Zhang, Z.; Li, P.; Zhang, Q.; Ding, X.; Zhang, W. Europium Nanospheres-Based Time-Resolved Fluorescence for Rapid and Ultrasensitive Determination of Total A fl atoxin in Feed. J. Agric. Food Chem. 2015, 63, 10313–10318.
  57. Xu, N.; Xiao, Y.; Xie, Q.; Li, Y.; Ye, J.; Ren, D. Occurrence of aflatoxin B1 in total mixed rations and aflatoxin M1 in raw and commercial dairy milk in northern China during winter season. Food Control 2021, 124, 107916.
  58. Xiong, J.; Xiong, L.; Zhou, H.; Liu, Y.; Wu, L. Occurrence of aflatoxin B1 in dairy cow feedstuff and aflatoxin M1 in UHT and pasteurized milk in central China. Food Control 2018.
  59. Zheng, N.; Sun, P.; Wang, J.Q.; Zhen, Y.P.; Han, R.W.; Xu, X.M. Occurrence of a fl atoxin M1 in UHT milk and pasteurized milk in China market. Food Control 2013, 29, 198–201.
  60. Center for Disease Control (CDC). Outbreak of Aflatoxin Poisoning Eastern and Central Provinces, Kenya, January–July 2004; 2004; Volume 53.
  61. Probst, C.; Njapau, H.; Cotty, P.J. Outbreak of an acute aflatoxicosis in Kenya in 2004: Identification of the causal agent. Appl. Environ. Microbiol. 2007, 73, 2762–2764.
  62. Azziz-baumgartner, E.; Lindblade, K.; Gieseker, K.; Rogers, H.S.; Kieszak, S.; Njapau, H.; Schleicher, R.; Mccoy, L.F.; Misore, A.; Decock, K.; et al. Case–Control Study of an Acute Aflatoxicosis Outbreak, Kenya, 2004. Environ. Health Perspect. 2005, 113, 1779–1784.
  63. Aydın, M.; Aydın, S.; Bacanlı, M.; Basaran, N. Aflatoxin levels in chronic hepatitis B patients with cirrhosis or hepatocellular carcinoma in Balıkesir, Turkey. J. Viral Hepat. 2015, 22, 926–935.
  64. Chu, Y.; Yang, H.; Wu, H.; Liu, J.; Wang, L.; Lu, S.; Lee, M.; Jen, C.; You, S.; Santella, R.M.; et al. Aflatoxin B 1 exposure increases the risk of cirrhosis and hepatocellular carcinoma in chronic hepatitis B virus carriers. Int. J. Cancer 2017, 141, 711–720.
  65. Lopez-Valdes, S.; Mario, M.C. The Relationship of Aflatoxin B1 and Hepatocellular Carcinoma: A Mini Review. J. Liver Res. Disord. Ther. 2017, 3, 5–6.
  66. Denissenko, M.F.; Koudriakova, T.B.; Smith, L.; Connor, T.R.O.; Riggs, A.D.; Pfeifer, G.P. The p53 codon 249 mutational hotspot in hepatocellular carcinoma is not related to selective formation or persistence of a ¯ atoxin B 1 adducts. Oncogen 1998, 17, 3007–3014.
  67. Verma, R.J. Aflatoxin Cause DNA Damage. Int. J. Hum. Genet. 2004, 4, 231–236.
  68. Wang, J.; Tang, L. Epidemiology of Aflatoxin Exposure and Human Liver Cancer. In Aflatoxin and Food Safety; Taylor & Francis Group, LLC, 2005; pp. 195–211.
  69. Obuseh, F.A.; Jolly, P.E.; Yi Jiang, F.M.B.S.; Waterbor, J.; Ellis, W.O.; Piyathilake, C.J.; Desmond, R.A.; Afriyie-Gyawu, E.; Phillips, T.D. Aflatoxin B1 albumin adducts in plasma and aflatoxin M1 in urine are associated with plasma concentrations of vitamins A and E. Int. J. Vitam. Nutr. Res. 2010, 80, 355–368.
  70. Chen, G.; Gong, Y.Y.; Kimanya, M.E.; Shirima, C.P. Comparison of urinary aflatoxin M1 and aflatoxin albumin adducts as biomarkers for assessing aflatoxin exposure in Tanzanian children. Biomarkers 2018, 23, 131–136.
  71. Ross, R.K.; Yuan, J.-M.; Yu, M.C.; Wogan, G.N.; Qian, G.-S.; Tu, J.-T.; Groopman, J.D.; Gao, Y.-T.; E.Henderson, B. Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma. Lancet 1992, 339, 944–946.
  72. Qian, G.; Ross, R.K.; Yu, M.C.; Yuan, J.; Gao, Y.; Henderson, B.E.; Wogan, G.N.; Groopman, J.D. A Follow-Up Study of Urinary Markers of Aflatoxin Liver Cancer Risk in Shanghai, People’s Republic Exposure and of China. Cancer Epidemiol. 1994, 3, 3–10.
  73. Guangxi, S.; Yeh, F.; Yu, M.C.; Mo, C.; Luo, S.; Tong, M.J.; Henderson, B.E. Hepatitis B Virus, Aflatoxins, and Hepatocellular Carcinoma in. Cancer Res. 1989, 49, 2506–2509.
  74. Tao, P.; Zhi-ming, L.I.U.; Tang-wei, L.I.U.; Le-qun, L.I.; Min-hao, P.; Xue, Q.I.N.; Lu-nam, Y.A.N.; Ren-xiang, L.; Zong-liang, W.E.I.; Lian-wen, W. Associated Factors in Modulating Aflatoxin B1–Albumin Adduct Level in Three Chinese Populations. Dig. Dis. Sci. 2005, 50, 525–532.
  75. Wan, L.; Hatch, M.; Chen, C.; You, S.; Lu, S.; Mei-huei, W.; Wus, W.; Wang, L.; Wang, Q. Aflatoxin Exposure and Risk of Hepatocellular Carcinoma In Taiwan. Int. J. Cancer 1996, 67, 620–625.
  76. Chen, C.; Wang, L.; Lu, S.; Wu, M.; You, S.; Zhang, Y.; Wang, L. Elevated Aflatoxin Exposure and Increased Risk of Hepatocellular Carcinoma. Hepatology 1996, 24, 38–42.
  77. Meng, E.C.H.; Hu, R.; Shi, X.; Zhang, S. Maize in China: Production Systems, Constraints, and Research Priorities; CIMMYT: Mexico D.F., Mexico, 2006; ISBN 9706481451.
  78. Sun, Z.; Chen, T.; Thorgeirsson, S.S.; Zhan, Q.; Chen, J.; Park, J.; Lu, P.; Hsia, C.C.; Wang, N.; Xu, L.; et al. Dramatic reduction of liver cancer incidence in young adults: 28 year follow-up of etiological interventions in an endemic area of China. Carcinogenesis 2013, 34, 1800–1805.
  79. FAO (Food and Agriculture Organization) Worldwide Regulations for mycotoxins in food and feed 2003. FAO Food Nutr. Pap. 2003, 81, 1–165.
  80. Wu, F.; Guclu, H. Aflatoxin Regulations in a Network of Global Maize Trade. PLoS ONE 2012, 7.
  81. EC European Commission, amending Regulation (EC) No 1881/2006 setting maximum levels for certain contaminants in foodstuffs as regards aflatoxins. Off. J. Eur. Union 2010, 165, 8–12.
  82. Zhang, H.; He, J.; Li, B. Aflatoxin Contamination and Research in China. In Aflatoxins-Detection, Measurement and Control; Torres-Pacheco, I., Ed.; InTech: Shanghai, China, 2009; pp. 22–36.
  83. European Commission (EC). Commission recommendation of 17 August 2006 on the presence of deoxynivalenol, zearalenone, ochratoxin A, T-2 and HT-2 and fumonisins in products intended for animal feeding. Off. J. Eur. Union 2006, 229, 7–8.
  84. Woo, C.S.J.; El-Nezami, H. Mycotoxins in Asia: Is China in danger? Qual. Assur. Saf. Crop. Foods 2015, 7, 3–25.
  85. CHEMLINKED National Food Safety Standard Limits of Mycotoxins in Foods. Available online: https://food.chemlinked.com (accessed on 23 June 2020).
  86. Tumukunde, E.; Ma, G.; Li, D.; Yuan, J.; Qin, L.; Wang, S. Current research and prevention of aflatoxins in China. World Mycotoxin J. 2020, 13, 121–138.
  87. Rasheed, U.; Wu, H.; Wei, J.; Ou, X.; Qin, P.; Yao, X.; Chen, H.; Chen, A.J.; Liu, B. A polyphasic study of Aspergillus section Flavi isolated from corn in Guangxi, China- a hot spot of aflatoxin contamination. Int. J. Food Microbiol. 2019, 310, 108307.
  88. Mamo, F.T.; Shang, B.; Selvaraj, J.N.; Wang, Y.; Liu, Y. Isolation and characterization of Aspergillus flavus strains in China. J. Microbiol. 2018, 56, 1–9.
  89. Yan, L.; Kang, Y.; Lei, Y.; Wan, L.; Huai, D.; Jiang, H.; Ren, X.; Liao, B. Genetic diversity of atoxigenic Aspergillus flavus isolates from peanut kernels in China. Oil Crop Sci. 2018, 3, 42–49.
  90. Lai, X.; Zhang, H.; Liu, R.; Liu, C. Potential for aflatoxin B 1 and B 2 production by Aspergillus flavus strains isolated from rice samples. Saudi J. Biol. Sci. 2015, 22, 176–180.
  91. Wei, D.; Zhou, L.; Selvaraj, J.N.; Zhang, C.; Xing, F.; Zhao, Y.; Wang, Y.; Liu, Y. Molecular characterization of atoxigenic Aspergillus flavus isolates collected in China. J. Microbiol. 2014, 52, 559–565.
  92. Yin, Y.; Lou, T.; Yan, L.; Michailides, T.; Ma, Z. Molecular characterization of toxigenic and atoxigenic Aspergillus flavus isolates, collected from peanut fields in China. J. Appl. Microbiol. 2009, 107, 1857–1865.
  93. Horn, B.W.; Dorner, J.W. Effect of nontoxigenic Aspergillus flavus and A. parasiticus on aflatoxin contamination of wounded peanut seeds inoculated with agricultural soil containing natural fungal populations. Biocontrol Sci. Technol. 2009, 19, 249–262.
  94. Abbas, H.K.; Zablotowicz, R.M.; Bruns, H.A.; Abel, C.A. Biocontrol of aflatoxin in corn by inoculation with non-aflatoxigenic Aspergillus flavus isolates. Biocontrol Sci. Technol. 2006, 16, 437–449.
  95. Alaniz Zanon, M.S.; Barros, G.G.; Chulze, S.N. Non-aflatoxigenic Aspergillus flavus as potential biocontrol agents to reduce aflatoxin contamination in peanuts harvested in Northern Argentina. Int. J. Food Microbiol. 2016, 231, 63–68.
  96. Atehnkeng, J.; Ojiambo, P.S.; Ikotun, T.; Sikora, R.A.; Cotty, P.J.; Bandyopadhyay, R. Evaluation of atoxigenic isolates of Aspergillus flavus as potential biocontrol agents for aflatoxin in maize. Food Addit. Contam.-Part A Chem. Anal. Control. Expo. Risk Assess. 2008, 25, 1264–1271.
  97. Pitt, J.I.; Hocking, A.D. Mycotoxins in Australia: Biocontrol of aflatoxin in peanuts. Mycopathologia 2006, 162, 233–243.
  98. Dorner, J.W.; Cole, R.J. Effect of application of nontoxigenic strains of Aspergillus flavus and A. parasiticus on subsequent aflatoxin contamination of peanuts in storage. J. Stored Prod. Res. 2002, 38, 329–339.
  99. Abbas, H.K.; Zablotowicz, R.M.; Horn, B.W.; Phillips, N.A.; Johnson, B.J.; Jin, X.; Abel, C.A. Comparison of major biocontrol strains of non-aflatoxigenic Aspergillus flavus for the reduction of aflatoxins and cyclopiazonic acid in maize. Food Addit. Contam. 2011, 28, 198–208.
  100. King, E.D.; Bassi, A.B.; Ross, J.C.; Druebbisch, B. An industry perspective on the use of “atoxigenic” strains of Aspergillus flavus as biological control agents and the significance of cyclopiazonic acid. Toxin Rev. 2011, 30, 33–41.
  101. Moore, G.G. Sex and recombination in aflatoxigenic Aspergilli: Global implications. Front. Microbiol. 2014, 5.
  102. Ehrlich, K.C. Non-aflatoxigenic Aspergillus flavus to prevent aflatoxin contamination in crops: Advantages and limitations. Front. Microbiol. 2014, 5.
  103. Olarte, R.A.; Horn, B.W.; Dorner, J.W.; Monacell, J.T.; Singh, R.; Stone, E.A.; Carbone, I. Effect of sexual recombination on population diversity in aflatoxin production by Aspergillus flavus and evidence for cryptic heterokaryosis. Mol. Ecol. 2012, 21, 1453–1476.
  104. Atehnkeng, J.; Donner, M.; Peter, S.; Ikotun, B.; Augusto, J.; Cotty, J.; Bandyopadhyay, R. Environmental distribution and genetic diversity of vegetative compatibility groups determine biocontrol strategies to mitigate aflatoxin contamination of maize by Aspergillus flavus. Microb. Biotechnol. 2016, 9, 75–88.
  105. Ehrlich, K.C.; Cotty, P.J. An isolate of Aspergillus flavus used to reduce aflatoxin contamination in cottonseed has a defective polyketide synthase gene. Appl. Microbiol. Biotechnol. 2004, 65, 473–478.
  106. Vaamonde, G.; Patriarca, A.; Ferna, V.; Comerio, R.; Degrossi, C. Variability of aflatoxin and cyclopiazonic acid production by Aspergillus section Flavi from different substrates in Argentina. Int. J. Food Microbiol. 2003, 88, 79–84.
  107. Zhang, C.; Selvaraj, J.N.; Yang, Q.; Liu, Y. A Survey of Aflatoxin-Producing Aspergillus sp. from Peanut Field Soils in Four Agroecological Zones of China. Toxins 2017, 9, 40.
  108. Yu, Z.; Yu, Z.; Jin, S.; Wang, L. Genetic diversity and toxin-producing characters of Aspergillus flavus from China. Biodivers. Sci. 2019, 27, 842–853.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
Video Production Service
Feedback