Advances in Mycotoxin Research: Public Health Perspectives

Aflatoxins, ochratoxins, fumonisins, deoxynivalenol, and zearalenone are of significant public health concern as they can cause serious adverse effects in different organs including the liver, kidney, and immune system in humans. These toxic secondary metabolites are produced by filamentous fungi mainly in the genus Aspergillus, Penicillium, and Fusarium. It is challenging to control the formation of mycotoxins due to the worldwide occurrence of these fungi in food and the environment. In addition to raw agricultural commodities, mycotoxins tend to remain in finished food products as they may not be destroyed by conventional processing techniques. Hence, much of our concern is directed to chronic health effects through long‐term exposure to one or multiple mycotoxins from contaminated foods. Ideally risk assessment requires a comprehensive data, including toxicological and epidemiological studies as well as surveillance and exposure assessment. Setting of regulatory limits for mycotoxins is considered necessary to protect human health from mycotoxin exposure. Although advances in analytical techniques provide basic yet critical tool in regulation as well as all aspects of scientific research, it has been acknowledged that different forms of mycotoxins such as analogs and conjugated mycotoxins may constitute a significant source of dietary exposure. Further studies should be warranted to correlate mycotoxin exposure and human health possibly via identification and validation of suitable biomarkers.     

Impact of mycotoxins on human health in developing countries

Adverse human health effects from the consumption of mycotoxins have occurred for many centuries. Although mycotoxin contamination of agricultural products still occurs in the developed world, the application of modern agricultural practices and the presence of a legislatively regulated food processing and marketing system have greatly reduced mycotoxin exposure in these populations. At the mycotoxin contamination levels generally found in food products traded in these market economies, adverse human health effects have largely been overcome. However, in the developing world, where climatic and crop storage conditions are frequently conducive to fungal growth and mycotoxin production, much of the population relies on subsistence farming or on unregulated local markets. The extent to which mycotoxins affect human health is difficult to investigate in countries whose health systems lack capacity and in which resources are limited. Aflatoxin B₁, the toxin on which major resources have been expended, has long been linked to liver cancer, yet its other effects, such as immune suppression and growth faltering previously observed in veterinary studies, are only now being investigated and characterized in human populations. The extent to which factors such as immune suppression contribute to the overall burden of infectious disease is difficult to quantify, but is undoubtedly significant. Thus, food safety remains an important opportunity for addressing current health problems in developing countries.     

Nutritional factors and colon cancer

During the last 2 decades, substantial progress has been made in understanding the relationship between dietary constituents and the development of colon cancer in man. Unlike studies of cancer among smokers and nonsmokers, nutritional epidemiologic studies are confronted with the inherent difficulty of assessing reasonably precise exposures. The lack of consistency between international correlation studies and case‐control studies does not necessarily negate a dietary etiology of colon cancer because these inconsistencies may have arisen, at least in part, from methodological limitations. Some of these deficiencies in epidemiological studies of diet and cancer have been corrected; recent case‐control studies demonstrated that high dietary fat is a risk factor for colon cancer development and that an overall increase in intake of foods high in fiber might decrease the risk for colon cancer. The results of epidemiologic studies may be assumed to present conservative estimates of the true risk for cancer associated with diet. The populations with high incidences of colon cancer are characterized by high consumption of dietary fat, which may be a risk factor in the absence of factors that are protective, such as whole‐grain cereals and of other high fiber. Laboratory‐animal model studies have shown that certain dietary lipids and fibers influence tumorigenesis in the colon. The data of metabolic epidemiological and laboratory‐animal model studies are sufficiently convincing with respect to the enhancement of colon cancer by type of fat and protection by certain dietary fibers.     

茶叶中真菌毒素污染的国内外研究概况

本文综述了国内外与茶叶真菌毒素污染有关的研究,结果表明,红茶、绿茶、白茶和黑茶都可能污染真菌和真菌毒素,应引起我国相关部门的重视。为降低真菌毒素污染茶叶的风险,建议加强茶叶毒素检测,普查各类茶叶真菌毒素污染情况;应用过程控制原理,筛选不产毒素菌株发酵黑茶,监测发酵过程,建立安全的黑茶发酵技术体系。     

Ochratoxin A and Human Health Risk: A Review of the Evidence

Ochratoxin A (OTA) is a mycotoxin produced by several fungal species including Aspergillus ochraceus, A. carbonarius, A. niger, and Penicillium verrucosum. OTA causes nephrotoxicity and renal tumors in a variety of animal species; however, human health effects are less well-characterized. Various studies have linked OTA exposure with the human diseases Balkan endemic nephropathy (BEN) and chronic interstitial nephropathy (CIN), as well as other renal diseases. This study reviews the epidemiological literature on OTA exposure and adverse health effects in different populations worldwide, and assesses the potential human health risks of OTA exposure. Epidemiological studies identified in a systematic review were used to calculate unadjusted odds ratios for OTA associated with various health endpoints. With one exception, there appears to be no statistically significant evidence for human health risks associated with OTA exposure. One Egyptian study showed a significantly higher risk of nephritic syndrome in those with very high urinary OTA levels compared with relatively unexposed individuals; however, other potential risk factors were not controlled for in the study. Larger cohort or case–control studies are needed in the future to better establish potential OTA-related human health effects, and further duplicate-diet studies are needed to validate biomarkers of OTA exposure in humans.     

Dietary exposure to mycotoxins of the Hong Kong adult population from a Total Diet Study

Dietary exposure of Hong Kong adults to mycotoxins and their metabolites including aflatoxins (AFs), ochratoxin A (OTA), fumonisins (FNs), deoxynivalenol (DON), acetyldeoxynivalenols (AcDONs) and zearalenone (ZEA) was estimated using the Total Diet Study (TDS) approach to assess the associated health risk to the local people. Sixty commonly consumed food items, collected in four seasons, were sampled and prepared as consumed. These mycotoxins were primarily found at low levels. The highest mean levels (upper bound) were: AFs, 1.50 µg kg^–1 in legumes, nuts and seed; OTA, 0.22 µg kg^–1 in sugars and confectionery; FNs, 9.76 µg kg^–1 in cereals and their products; DON and AcDONs, 33.1 µg kg^–1 in cereals and their products; and ZEA, 53.8 µg kg^–1 in fats and oils. The estimated dietary exposures of Hong Kong adults to the mycotoxins analysed were well below the respective health-based guidance values, where available. For AFs, the upper-bound exposure for high consumers is 0.0049 µg kg bw^–1 day^–1, which was estimated to contribute to about 7.7 (< 1%) of liver cancer cases when compared with 1222 liver cancer cases per year in Hong Kong. The percentage contributions of the estimated 95th percentile dietary exposures (lower and upper bound) to the health-based guidance values of individual mycotoxins were: ochratoxin A, 3.6–9.2%; fumonisins, 0.04–8.5%; deoxynivalenol and acetyldeoxynivalenols, 21.7–28.2%; and zearalenone 3.3–34.5%. The findings indicate that dietary exposures to all the mycotoxins analysed in this study were unlikely to pose an unacceptable health risk to the Hong Kong population.     

农产品真菌毒素混合污染与累积风险评估研究进展

真菌毒素混合污染危害人畜及农作物健康。目前真菌毒素累积风险评估研究多针对常见的混合污染物,且国内研究较少。此外,毒理学数据及居民消费数据较缺乏,科学的采样方法及人体暴露量的测定方法有待改进。本文阐述了现有的农产品真菌毒素混合污染物的累积风险评估方法以及存在的问题,在危害描述方面,不同含量的真菌毒素混合物在不同动物细胞的体内或体外实验中产生的联合毒性存在差异;在暴露评估方面,基于概率评估的膳食暴露评估和基于生物标记物的暴露评估方法研究日益增多;在风险描述方面,已报道的针对真菌毒素的方法包括危害指数(hazard index,HI)和联合暴露限量值指数(combined margin of exposure index,MOET)。提出了开展真菌毒素混合污染风险评估的必要性,以期为保护人体健康、制定真菌毒素混合污染物限量标准和健康指导值提供基础。     

Exposure,Occurrence, and Chemistry of Fumonisins and their Cryptic Derivatives

Fumonisins are mycotoxins mainly produced by Fusarium proliferatum and Fusarium verticillioides. Because of their wide distribution, the potential health hazard, and economic significance, they are considered one of the most important mycotoxin classes. Epidemiological evidence suggests a relationship between the Fusarium load in corn, exposure to fumonisins, and esophageal cancer. However, mechanisms of actions of fumonisins are not yet fully resolved and epidemiological studies suffer from various confounding factors. Correspondingly, the most relevant congener of the fumonisin family (fumonisin B₁) has been classified as possibly carcinogenic to humans and maximum limits have been set for corn and corn‐based products. However, many non‐corn‐based products are also susceptible to fumonisin contamination. Indeed, some of them contain very high amounts of fumonisins, but enter the market legally. Furthermore, fumonisin exposure of consumers is probably consistently being underestimated because only a fraction of fumonisins can be detected by routine analysis. The bioavailability and toxicity of most nondetectable (cryptic) forms has not been resolved. In this work, we review the developments of cancer research into fumonisins since their discovery in 1988 until today and provide an overview of the contributions of various foodstuffs to fumonisin exposure, including those products that have been largely neglected in the past. In conclusion, (1) corn remains the principal source of fumonisin ingestion, but fumonisins in non‐corn‐based commodities require continuous monitoring; (2) cryptic fumonisins should be included in risk assessment studies; and (3) certain population groups (for example children) may suffer from enhanced exposure and could face increased health risks.     

Utilising an LC-MS/MS-based multi-biomarker approach to assess mycotoxin exposure in the Bangkok metropolitan area and surrounding provinces

Human exposures to mycotoxins through dietary intake are a major health hazard and may result in various pathophysiological effects. Although Thailand is a country at increased risk due to its climatic conditions, no comprehensive dataset is available to perform proper exposure assessment of its population with regard to mycotoxins. Therefore, this pilot study was conducted to investigate and evaluate the exposure levels of major mycotoxins (aflatoxin B₁, ochratoxin A, fumonisins, zearalenone and trichothecenes). Sixty first-morning urine samples were collected from healthy volunteers who live in the Bangkok metropolitan area and surrounding provinces (Pathumthani, Nonthaburi, Samutprakarn and Samutsakorn). Urine samples were analysed by a LC-MS/MS-based multi-biomarker method following a so-called ‘dilute and shoot’ approach. Results generally indicated low mycotoxin exposures in most individuals through the determination of the four biomarkers that were detected in urine samples, i.e. aflatoxin M₁, ochratoxin A (OTA), as well as the deoxynivalenol (DON) metabolites DON-3-glucuronide and DON-15-glucuronide in 10 of 60 individuals. The maximum concentrations were used to estimate the daily intake confirming that none of the individuals exceeded the tolerable daily intake (TDI) of DON (maximum 26% of TDI) or OTA (maximum 22% of TDI). However, the maximum exposure of aflatoxin B₁, estimated to be 0.91 µg (kg bw)^–1 day^–1, should raise some concerns and suggests further studies utilising a more sensitive method. Low exposure to Fusarium toxins was also confirmed by the absence of zearalenone, α-zearalanol, β-zearalanol and zearalenone-14-glucuronide as well as T-2 toxin, HT-2 toxin, nivalenol and free DON. This is the first multi-mycotoxin biomarker study performed in Southeast Asia.     

A review of postharvest approaches to reduce fungal and mycotoxin contamination of foods

Contamination of agricultural and food products by some fungi species that produce mycotoxins can result in unsafe food and feed. Mycotoxins have been demonstrated to have disease‐causing activities, including carcinogenicity, immune toxicity, teratogenicity, neurotoxicity, nephrotoxicity, and hepatotoxicity. Most of mycotoxins are heat stable and cannot be easily destroyed by conventional thermal food processing or domestic cooking methods. Postharvest approaches to prevent growth of mycotoxin‐producing fungi and detoxify mycotoxins from contaminated food are important topics in food safety research. Physical, chemical, and biological methods have been applied to prevent fungal growth or mycotoxin production, or to reduce mycotoxin content in the postharvest period and contribute toward mitigating against the effects of mycotoxins on human health. This literature review aims to evaluate postharvest approaches that have been applied to control both fungi growth and mycotoxin content in food and discuss their potential for upscaling to industrial scale.     

Keeping mycotoxins away from the food: Does the existence of regulations have any impact in Africa?

Following the discovery of aflatoxins in the early 1960s, there have been many studies leading to the uncovering of many mycotoxins and the understanding of associated health effects in animals and humans. Consequently, there has been a global increase in the number of countries with mycotoxin regulations in foods. However, many African countries have only regulations for aflatoxins (or a few other mycotoxins) in specific foods, or no regulations at all. This paper critically reviews the challenges thwarting the establishment of mycotoxin regulations and their impacts on human dietary mycotoxin exposure in Africa. Mycotoxin regulatory limits for different countries are compared with mycotoxin tolerable daily intakes established by international food safety bodies taking into account consumption patterns. The agrarian setup, food insecurity, and mycotoxin analytical challenges in African countries are discussed; and more feasible mycotoxin dietary exposure reduction strategies are proposed.     

茶叶中真菌毒素风险评估及防控研究进展

茶叶在国内外有着广泛的消费基础,对人体有益作用明显,但生产加工过程中茶园管理、鲜叶采摘、茶叶加工、流通和储存不当易造成真菌毒素污染,影响茶叶品质及消费者健康。开展茶叶真菌毒素风险评估研究及控制对于促进茶叶产业健康持续发展有重要意义,研究显示通过饮用茶叶摄入真菌毒素健康风险较低。本文综述了茶叶中真菌毒素污染来源、危害、安全限值设置及防控措施,重点对茶叶中真菌毒素检测方法、迁移溶出规律、常用暴露评估方法和风险描述进行归纳梳理。在此基础上,分析茶叶真菌毒素暴露风险评估存在的问题,对其研究方向进行展望,以期为茶叶中真菌毒素的评估和污染控制领域后续研究提供参考。     

Food Safety and Increasing Hazard of Mycotoxin Occurrence in Foods and Feeds

The possible hazard of mycotoxin occurrence in foods and feeds and some food-borne mycotoxicoses is reviewed. Management of the risk of mycotoxin contamination using some useful preventive measures against mycotoxin contamination of foods/feeds during pre- and post-harvesting periods is considered. The physical and chemical methods of mycotoxin decontamination of foods/feeds are briefly described. The use of various feed additives as a method for prevention of the adverse effects of mycotoxins is reviewed. The processing of various foods and feeds is considered in a view to possible mycotoxin decontamination. The necessary hygiene control and risk assessment in regard to mycotoxin contamination of foods and feeds in addition to some useful prophylactic measures are briefly described. A short reference is made concerning the most successful methods of veterinary hygiene control in order to prevent a possible entering of some mycotoxins in commercial channels with a view to human health.     

Coffee and cancer risk,epidemiological evidence,and molecular mechanisms

Although early studies suggested that coffee consumption might increase risk of some cancers, more comprehensive epidemiological and experimental data now generally indicate either neutral or beneficial effects. In this review, we summarize the current evidence for associations between breast, prostate, colorectal, and liver cancers and the consumption of coffee, and discuss the experimental evidence for potential chemopreventive mechanisms of coffee and coffee constituents. The epidemiological evidence consistently indicates that coffee protects against liver cancer, and also point toward protective effects for risk of colorectal cancers (with relative risks of 0.50 (95% CI: 0.42–0.59) and 0.83 (95% CI: 0.75–0.92), respectively, in the most recent meta‐analyses). There seems to be no association between the overall risk of breast and prostate cancer and coffee intake. However, for subgroups such as postmenopausal breast cancers, advanced prostate cancers, and breast and prostate cancer survivors, an inverse association with coffee intake is indicated. Potential mechanisms for chemopreventive effects of coffee phytochemicals includes inhibition of oxidative stress and oxidative damage, regulation of DNA repair, phase II enzymatic activity, apoptosis, inflammation, as well as having antiproliferative, antiangiogenetic effects and antimetastatic effects. The experimental evidence for effects of coffee and coffee constituents on each of these processes is discussed.     

Occurrence and preventive strategies to control mycotoxins in cereal‐based food

Mycotoxins contamination in cereal‐based food is ubiquitous according to systematic review of the scientific documentation of worldwide mycotoxin contamination in cereal and their products between 2008 and 2018, thus representing food safety issue especially in developing tropical countries. Food processing plays a vital role to prevent mycotoxin contamination in food. Therefore, it is with great urgency to develop strategies to inhibit fungi growth and mycotoxin production during food processing. This review begins by discussing physicochemical properties of five most common mycotoxins (aflatoxins, fumonisins, ochratoxins, deoxynivalenol, and zearalenone) found in cereal grains, regulation for mycotoxins in food, and their potential negative impact on human health. The fate of mycotoxins during major cereal‐based food processing including milling, breadmaking, extrusion, malting, and brewing was then summarized. In the end, traditional mitigation strategies including physical and chemical and potential application of biocontrol agent and essential oil nanoemulsions that can be applied during food processing were discussed. It indicated that no single method is currently available to completely prevent mycotoxin contamination in cereal foods.     

Natural Occurrence of Mycotoxins in Food and Feed: Pakistan Perspective

Fungi are commonly present in the environment and can grow under favorable conditions on an extensive variety of substrates. During harvesting, handling, storage, and distribution, agricultural commodities are subjected to infection by toxigenic molds, which may cause spoilage and produce toxic metabolites called mycotoxins. Fungal contamination of various food commodities with consequent exposure of the community to mycotoxins is a hazard that may exist depending on environmental factors, crop health, and soil conditions. Mycotoxins represent serious consequences due to substantial economic loss and risk to health. The environmental conditions of Pakistan with its mostly warm temperature are conducive to growth of toxigenic fungi resulting in mycotoxin production in different food items. Moreover, the poor conditions of storage and deficiency in regulatory measures in food quality control worsen the situation in the country. This review encompasses mycotoxin contamination of food and feed in Pakistan. High concentrations of mycotoxins are found in some commodities that are used on a daily basis in Pakistan, which may be a concern depending on dietary variety and health conditions of individuals in the population. Therefore, the mycotoxin contamination of foodstuff with exceeding levels represents a serious health hazard for the local population. There is a need to conduct more studies to analyze mycotoxin occurrence in all types of food commodities throughout the country. For consumer safety and the country's economy, the regulatory authorities should take into account this issue of contamination, and control strategies should be implemented and the quality control system of food improved.     

葡萄酒中赭曲霉毒素A污染情况及其分析方法的研究进展

葡萄酒作为一种酒精饮料,对众多国家的经济贡献是显著的。然而,该商品容易被某些真菌产生的霉菌毒素所污染,其中最受关注的是产赭曲霉毒素A(ochratoxin A, OTA)的炭黑曲霉。赭曲霉毒素A是葡萄酒中主要存在的霉菌毒素,严重影响着人类的健康。因此,葡萄酒的风险监测和暴露研究至关重要。本研究重点阐述了OTA的生物合成途径及其调控机制,同时,介绍了酿酒过程中OTA的变化情况以及控制和检测OTA的方法,旨在为保证葡萄酒产品的质量安全提供一些理论参考。     

Famine exposure during early life and risk of hypertension in adulthood: A meta-analysis

ABSTRACT

Background: Many epidemiologic studies have explored the association between famine exposure and the risk of hypertension, but the results remain controversial. Objective: A meta-analysis was performed to determine the association between early life famine exposure, fetal famine exposure, and childhood famine exposure and risk of hypertension. Methods: A literature search was performed in PubMed, Web of science, Embase, and China National Knowledge Infrastructure for relevant articles published up to October 2016. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Results: Sixteen studies from 14 articles for early life famine exposure, 11 studies from 10 articles for fetal famine exposure, and 10 studies from 8 articles for childhood famine exposure were included in our meta-analysis. Compared with unexposed group, the pooled RRs were (1.26; 95% CI, 1.11–1.44), (1.27; 95% CI, 1.08–1.49), and (1.32; 95% CI, 1.15–1.52) for early life famine exposure, fetal famine exposure, and childhood famine exposure, respectively. In subgroup analyses, the above-mentioned associations were consistent in cohort studies, and studies conducted in Asia. Conclusion: This meta-analysis confirmed the association between exposure to famine in early life and increased risk of hypertension in adulthood. Prevention of malnutrition during early life is an appropriate recommendation to prevent hypertension.     

Distribution of mycotoxins and risk assessment of maize consumers in five agro-ecological zones of Nigeria

Many individuals are not only food insecure but chronically exposed to high levels of mycotoxins through their diets in many developing countries. Seventy composite samples of stored maize grains were collected from farmers’ storage structures in five agro-ecological zones (AEZs) of Nigeria where maize is predominantly produced between August 2011 and February 2012. The grains were analysed for mycotoxin contamination with the liquid chromatography tandem mass spectrometry method and mycotoxin occurrence maps constructed from the database of the distribution of the toxins. A risk assessment was also carried out in order to provide information on the extent of human exposure to the toxins. Twelve regulated mycotoxins with negative economic and public health consequences were detected in the maize grains across the AEZs at concentrations exceeding the maximum allowable limits including AFM₁ that was detected for the first time in Nigerian maize. There is a high risk of contamination of the stored grains by Nigerian consumers especially in the Derived and Southern Guinea Savannas, resulting in a national burden of between 126.85 and 38,682.29 DALYs. Intervention strategies are therefore needed across the AEZs to ensure that safe and wholesome foods are made available to the populace.