Performing Department
Food Science
Non Technical Summary
Mycotoxins are secondary metabolites of fungi that colonize our food crops, which can have toxic and carcinogenic effects to the humans and animals that consume those crops. It is not precisely known why the fungi that infect food crops produce these toxins. Various hypotheses have been put forth, such as that the mycotoxins are a virulence factor that allow the fungi to more successfully colonize crop plants, or that the fungi produce mycotoxins as a means of sequestering free radicals that the crop plants may emit in response to fungal infection.Regardless, the effects to human and animal health have been severe, and have been documented for centuries. Since the Middle Ages, humans have been affected by mycotoxicoses such as "St. Anthony's Fire" - a gangrenous disease associated with the consumption of moldy rye infected by the fungus Claviceps purpurea, which produces highly toxic ergot alkaloids (CAST 2003). However, it was not until 1960 that humans discovered that food molds produced toxins. In that year, aflatoxin was first identified and characterized - a carcinogenic mycotoxin produced by the fungi Aspergillus flavus and A. parasiticus, commonly contaminating corn, peanuts, and other nuts in warm climates worldwide. Aflatoxin was connected with the deaths of over 100,000 turkey poults that consumed contaminated peanut meal in the United Kingdom (Kensler et al. 2011).Today, it is known that aflatoxin is the most potent naturally occurring human liver carcinogen. The International Agency for Research on Cancer (IARC) has classified "Naturally occurring mixes of aflatoxins" as a Group 1 human carcinogen (IARC 1993). Additionally, aflatoxin has been associated with acute toxicity leading to liver failure and the deaths of hundreds of Kenyans (Strosnider et al. 2006), immune system dysfunction, and growth impairment in children (Khlangwiset et al. 2011). In a World Health Organization (WHO) evaluation of all the food contaminants evaluated for their contribution to human disease worldwide, aflatoxin ranked the highest among chemicals and toxins for its global burden of human disease, in terms of disability-adjusted life years, for liver cancer alone (Havelaar et al. 2015). If the other adverse health effects associated with aflatoxin consumption were included in this analysis, the global burden of human disease would be even greater.Aside from aflatoxin and ergot alkaloids, other mycotoxins of importance at the nexus of agricultural production and human health effects include fumonisin (produced by Fusarium verticillioides and F. proliferatum), deoxynivalenol (DON or vomitoxin, produced by F. graminearum and F. culmorum) and its acetylated derivatives, and ochratoxin A (produced by Penicillium verrucosum A. ochraceus, A. carbonarius). The human health effects of these mycotoxins are reviewed in Wu et al. (2014).Taken together, these mycotoxins constitute a significant economic and human health problem in Michigan, the United States, and throughout the world. In Michigan, which generally has a temperate-to-cool climate, the main mycotoxins of concern are DON (vomitoxin) in corn and small cereal grains such as wheat, barley, and oats; and ochratoxin A (OTA) in multiple foodstuffs. This is because F. graminearum and P. verrucosum, the fungi that produce these toxins, are cool-weather fungi. In the US more broadly, all of these mycotoxins cause economic loss to farmers; through contaminated food lots being rejected at grain elevators and food handlers, and through adverse health effects to livestock and poultry. Fortunately, in Michigan and the US, there is not a large burden of human disease caused by dietary mycotoxins; because the Food and Drug Administration (FDA) has set action levels for maximum allowable aflatoxin in human food and various animal feeds, and industry guidelines for other mycotoxins. Thus, instead of mycotoxin-contaminated foodstuffs entering the human food supply, they are rejected (causing economic loss to Michigan and US farmers) or sold for animal feed or alternative uses.In low- and middle-income countries, however, even if regulations for maximum allowable levels of mycotoxins in food exist, there is often little enforcement of these rules - particularly in nations where subsistence farming is common. Thus, mycotoxin consumption leads directly to human disease. Dietary mycotoxins pose the greatest risk to human populations living in warm climates (aflatoxin and fumonisin are common) who consume high amounts of corn and peanuts. This characterizes many populations in sub-Saharan Africa, Central America, and Southeast Asia. Liu and Wu (2010) found that over 100,000 liver cancer cases per year could be due to aflatoxin consumption, and that most of these cases would occur in these high-risk regions of the world. A large proportion of childhood stunting and other forms of child growth impairment could also be attributed to early childhood mycotoxin exposure (Khlangwiset et al. 2011, Chen et al. 2017).Moreover, there is evidence that if current patterns of climate change continue, mycotoxin problems could increase in Michigan, the United States, and worldwide. In particular, aflatoxin and fumonisin, warm-weather mycotoxins, are expected to increase in prevalence in crops. It is worth noting that in the last few decades, in years in which summers are unusually hot and dry, aflatoxin problems (normally confined to southern states) have spread to the Corn Belt (Mitchell et al. 2016). This poses potentially enormous economic losses for US farmers, and similar patterns could occur worldwide. Relevant to Michigan, more extreme precipitation and drought events could predispose crops to DON contamination (Miller 2008). In industrial nations, increases in mycotoxins will primarily affect growers economically; while in low- to middle-income countries, population health could be compromised.This proposed project will focus on interventions that reduce the risk of mycotoxins and their adverse effects (economic and health) in the US and global food supply. As more thoroughly described below, the project has several objectives:Objective 1: Conduct human health risk assessments of the current state of mycotoxins and their presence in the food supply, in the US and worldwide.Objective 2: Evaluate the efficacy, cost-effectiveness, and feasibility of different mycotoxin control strategies in the US and in low-income settings worldwide.Objective 3: Estimate the changes in concentration and geographic spread of aflatoxin contamination in the US corn crop in the near future, given predictions of climatic factors (daily temperature and precipitation) across all counties.The beneficiaries of this research will be farmers, food producers/distributors, and consumers in Michigan, the United States, and worldwide. Reducing the mycotoxin problem will improve economic return to crop growers, and will ensure a safer food supply for humanity.
Animal Health Component
0%
Research Effort Categories
Basic
25%
Applied
70%
Developmental
5%
Goals / Objectives
This proposed project will focus on interventions that reduce the risk of mycotoxins and their adverse effects (economic and health) in the US and global food supply. The project has several objectives:Objective 1: Conduct human health risk assessments of the current state of mycotoxins and their presence in the food supply, in the US and worldwide.Objective 2: Evaluate the efficacy, cost-effectiveness, and feasibility of different mycotoxin control strategies in the US and in low-income settings worldwide.Objective 3: Estimate the changes in concentration and geographic spread of aflatoxin contamination in the US corn crop in the near future, given predictions of climatic factors (daily temperature and precipitation) across all counties.The beneficiaries of this research will be farmers, food producers/distributors, and consumers in Michigan, the United States, and worldwide. Reducing the mycotoxin problem will improve economic return to crop growers, and will ensure a safer food supply for humanity.
Project Methods
Objective 1: Conduct human health risk assessments of the current state of mycotoxins and their presence in the food supply, in the US and worldwide.Sub-Objective 1.1: Conduct a human health risk assessment of fumonisin worldwide; specifically in children's diets, to examine the link between fumonisin exposure and child growth impairment.The PI's currently funded work from the Bill & Melinda Gates Foundation has allowed data collection in Tanzanian and Nepalese children's cohorts of how fumonisin exposure is correlated with child growth, controlling for macro- and micronutrient status, socioeconomic factors, and microorganisms found in stool. First, the PI and her research team will estimate a dose-response curve from combined data on fumonisin and child growth impairment: the data from her BMGF project as well as from Shirima et al. (2015). Then she will collect data on fumonisin levels in foods and urinary fumonisin biomarkers in populations worldwide to estimate global burden of child growth impairment due to fumonisin.Sub-Objective 1.2: Conduct a human health risk assessment of DON worldwide, using as the benchmarks the new Codex Alimentarius guideline of 1 milligram DON per kilogram food and the Joint Expert Committee on Food Additives tolerable daily intake of 1ug DON perkg bodyweight per day.By conducting a literature search in the vein of Liu and Wu (2010), DON contamination levels in wheat in different parts of the world and DON exposure in different populations worldwide will be estimated. The World Health Organization (WHO) Global Environment Monitoring Programme (GEMS) database contains information on amounts of foodstuffs consumed by adults in 17 broad regions of the world (nations matched by similarities of diets). The dietary exposure equation to estimate DON exposure is: ADDDON = CDON * IR / bw, where ADDDON = average daily dose of DON, CDON = concentration of DON in wheat, IR = intake rate of wheat, and bw = bodyweight. First, a baseline risk assessment to determine the current state of DON-related risk worldwide will be conducted; then a risk assessment assuming that all nations adopted the Codex DON guidelines and removed from human consumption the wheat that would otherwise be contaminated with DON above these guidelines.Objective 2: Evaluate the efficacy, cost-effectiveness, and feasibility of different mycotoxin control strategies in the US and in low-income settings worldwide.Sub-Objective 2.1: Compile a comprehensive list of available and "in development" interventions that control mycotoxins in pre-harvest, post-harvest, and dietary settings; and evaluate the extent to which they reduce mycotoxins or their bioavailability.While Khlangwiset and Wu (2010) list a number of interventions that can reduce aflatoxin and other mycotoxins in the food supply, these lists do not include the most recent discoveries of technologies and integrated methods to reduce mycotoxins, such as RNA interference (RNAi) methods genetically engineered into crops that use host-induced gene silencing (HIGS) to prevent invading fungi from producing mycotoxins. Additionally, literature searches will be conducted on the interventions listed in the sources above to determine the extent to which mycotoxins are reduced.Sub-Objective 2.2: Conduct a cost-effectiveness analysis of these interventions in industrial vs. resource-poor settings.In industrial nations, cost-effectiveness will be evaluated based on the cost of the intervention compared with the economic savings through improved acceptance of crop lots to farmers.In the US,grain elevators and food handlers employ "discount schedules" associated with differing levels of mycotoxins in the farmers' lots. An example of a discount schedule for aflatoxin in corn is given in Mitchell et al. (2016). The economic benefit from the lower mycotoxin levelswill be compared with the cost of adopting the intervention. Thus, the net value of adoption of each intervention will be elucidated. In resource-poor settings, cost-effectiveness will be assessed based on the disability-adjusted life years saved from implementing the intervention in the population, vs. the cost of the intervention for the population. The World Health Organization metric for evaluating the cost-effectiveness of interventions in low-income nations will be used. WHO designates a public health intervention "cost-effective" if the cost of the intervention (in a population) is less than the product of the total DALYs saved by the intervention and the gross domestic product (GDP) per capita of that population. This sub-objective will focus on aflatoxin mitigation, since aflatoxin is the one mycotoxin for which reductions in exposure can be directly translated into liver cancer risk reduction (Liu and Wu 2010, Wu and Khlangwiset 2010a), and hence into DALYs. This analysis will be done for each aflatoxin control strategy.Sub-Objective 2.3: Assess the technical feasibility of each of the interventions outlined in this Objective, for industrial vs. resource-poor settings. - A framework developed by Gericke et al. (2005) and used for several aflatoxin control strategies in Wu and Khlangwiset (2010b) will be used to assess the technical feasibility of each of the mycotoxin control strategies identified above.Objective 3: Estimate the changes in concentration and geographic spread of aflatoxin contamination in the US corn crop in the near future, given predictions of climatic factors (daily temperature and precipitation) and aflatoxin-related insurance claims by corn growers across all counties.Sub-Objective 3.1: Develop and refine a predictive model of how aflatoxin-related insurance claims are affected by interventions (such as Bt corn planting), maximum and minimum temperature ranges across the corn planting season, and soil moisture as determined by the Palmer Z indices of different months (accounting for drought, precipitation, and relative humidity).The PI's current USDA/Purdue fungal pathosystems program grant has allowed collection of data from the USDA Risk Management Agency (RMA) on aflatoxin-related insurance claims among corn growers in the US. The prevalence of aflatoxin-related insurance claims by crop reporting district will be the dependent variable of these analyses; while the independent variables include temperature, moisture, and use of interventions such as Bt corn. Data on Bt corn planting (as a possible means to reduce aflatoxin through reduced insect damage) and biocontrol adoption will be gathered from the USDA National Agricultural Statistical Survey (NASS) or purchased from Kynetec Ltd. Data on daily maximum and minimum temperatures, precipitation, and Palmer Z indices by month will be gathered from the National Oceanic and Atmospheric Administration (NOAA). A multilinear regression model will be developed to assess the association of aflatoxin insurance claims as a function of these variables.Sub-Objective 3.2: Predict the geographic spread of aflatoxin problems as measured by likely aflatoxin-related insurance claims based on above model, using predictive climate data from NOAA.NOAA provides predictive daily temperatures and precipitation levels for each county of the United States till 2030, the last year of this project's interest. In that time, based on the predictive model for aflatoxin-related problems developed in the previous sub-objective, the changes in aflatoxin-related insurance claims for corn-growing counties across the US will be estimated. This will provide a sense of whether aflatoxin problems will increase or decrease in the near future in the US, as well as how the geographical spread is likely to change based on climatic factors.