CONTROLLING MYCOTOXINS IN THE FOOD SUPPLY IN THE UNITED STATES AND WORLDWIDE

• Sponsoring Institution: National Institute of Food and Agriculture
• Project Status: COMPLETE
• Funding Source: HATCH
• Reporting Frequency: Annual
• Accession No.: 1014542
• Project Start Date: Dec 1, 2017
• Project End Date: Nov 30, 2022
• Program Code: [(N/A)]- (N/A)

Recipient Organization
MICHIGAN STATE UNIV
(N/A)
EAST LANSING,MI 48824

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

70%

Research Effort Categories

Basic

25%

Applied

70%

Developmental

5%

Classification

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
712	5010	1150	100%

Knowledge Area
712 - Protect Food from Contamination by Pathogenic Microorganisms, Parasites, and Naturally Occurring Toxins;

Subject Of Investigation
5010 - Food;

Field Of Science
1150 - Toxicology;

Keywords

mycotoxins

economics

public health

risk assessment

climate change

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.

Progress 10/01/20 to 09/30/21

Outputs
Target Audience:Target audiences for our research on this grant include: 1. Fellow researchers at the nexus of agriculture, food safety, and human and animal health. 2. Policymakers in this nexus (ag-food-health). 3. Stakeholders along food supply chains - farmers, processors, food industries, consumers - concerned about food safety. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?I am grateful to have supported and trained 2 PhD students on this project during this time period, who have had the chance to learn about food safety, risk assessment, and the economics of strategies to reduce contaminants in food to protect human and animal health. My students, colleagues, and I have had the chance to present this work at several venues during the year Oct 2020 - Sept 2021, including: US Environmental Protection Agency, Entomological Society of America, Society for Risk Analysis, International Union of Pure and Applied Chemistry, and various roundtables and talks at Michigan State University. How have the results been disseminated to communities of interest?We have published multiple papers anda book chapter, and our work has been featured in multiple news articles and media appearances ranging from the American Association for the Advancement of Science (AAAS) to Detroit News (WXYZ-Detroit) to MSN Lifestyle to Prevention magazine. We have also had the chance to give presentations in all the venues and conferences described above. What do you plan to do during the next reporting period to accomplish the goals?In this next reporting period, we hope to continue our work on examining non-cancer health risks of total aflatoxins (B1, B2, G1, G2) and aflatoxin M1; as well as on strategies to reduce moisture along food supply chains to reduce microbial pathogens (including toxigenic fungi).We hope to publish on the findings of our projected spread of aflatoxin in US corn in the years 2031-2040.

Impacts
What was accomplished under these goals? From October 1, 2020 to September 30, 2021, we have accomplished the following under each of these objectives: 1. Objective 1: We have conducted human health risk assessments of aflatoxin-related immunomodulation, cassava cyanide-related cognitive impairment in children, and aflatoxin M1 in milk worldwide. 2. Objective 2: We have evaluated the efficacy, cost-effectiveness, and feasibility of United Nations Codex Alimentarius Commission guidelines on deoxynivalenol (DON) in food on reducing DON exposure in global populations, as well as a simple wetting method to reduce cyanide in cassave; and have conducted a review of strategies to reduce aflatoxin in food worldwide. 3. Objective 3: We are preparing a paper on the projected spread of aflatoxin-related risks in corn in the United States as a function of near-term climatic conditions (maximum daily temperatures, rainfall).

Publications

• Type: Journal Articles Status: Published Year Published: 2020 Citation: Grace D, Wu F, Havelaar A (2020). Foodborne diseases from milk and milk products in developing countries: Review of causes and health and economic implications. Journal of Dairy Science 103:9715-29.
• Type: Journal Articles Status: Published Year Published: 2020 Citation: Wu F, Rodricks JV (2020). Forty years of food safety risk assessment: A history and analysis. Risk Analysis 40:2218-30.
• Type: Journal Articles Status: Published Year Published: 2021 Citation: Chen C, Wu F (2021). Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) colonization and infection among livestock workers and veterinarians: A systematic review and meta-analysis. Occupational and Environmental Medicine 78:530-40.
• Type: Journal Articles Status: Published Year Published: 2021 Citation: Ademola O, Saha Turna N, Liverpool-Tasie L, Obadina A, Wu F (2021). Food Processing and Mycotoxin Reduction in Maize-Based Products: Evidence from Lactic Acid Fermentation in Southwest Nigeria. Food Control 121:107620.
• Type: Journal Articles Status: Published Year Published: 2021 Citation: Saha Turna N, Wu F (2021). Aflatoxin M1 in milk: Global occurrence, intake, and exposure assessment. Trends in Food Science and Technology 110:183-92.
• Type: Journal Articles Status: Published Year Published: 2021 Citation: Chen C, Frank K, Wang T, Wu F (2021). Global wheat trade and Codex Alimentarius guidelines for deoxynivalenol: A mycotoxin common in wheat. Global Food Security 29:100538.
• Type: Journal Articles Status: Published Year Published: 2021 Citation: Ye Z, Wu F, Hennessy DA (2021). Environmental and Economic Concerns Surrounding Restrictions on Glyphosate Use in Corn. Proceedings of the National Academy of Sciences 118:e2017470118.
• Type: Journal Articles Status: Published Year Published: 2021 Citation: Saha Turna N, Wu F (2021). Estimation of tolerable daily intake (TDI) for non-carcinogenic effects of aflatoxin. Risk Analysis, DOI:10.1111/risa.13770.
• Type: Journal Articles Status: Published Year Published: 2021 Citation: Chen C, Kashala-Abotnes E, Banea Mayambu J-P, Mumba Ngoyi D, Tshala-Katumbay D, Mukeba D, Kunya M, Boivin MJ, Wu F (2021). Cost-effectiveness of a wetting method intervention to reduce cassava cyanide-related cognitive impairment in children. Nature Food 2:469-72.
• Type: Book Chapters Status: Published Year Published: 2021 Citation: Wu F (2021). Foodborne Mycotoxins. In: Foodborne Infections and Intoxications, 5th Ed. Morris JG and Vugia DJ, Eds., Academic Press, Elsevier, London, United Kingdom, pp. 439-454.

Progress 10/01/19 to 09/30/20

Outputs
Target Audience:Target audiences reached by my efforts in the past year have included: 1. US governmental agencies interested in food safety, agriculture, and protection of food workers: USDA, FDA, and CDC. 2. Academic and scholastic communities who work in the areas of risk analysis, food safety, toxicology, mathematical modeling, and health economics. 3. Industries and their associated groups, particularly the agricultural biotechnology and food production / processing industries. 4. Agricultural and food stakeholders and the general public for interest in food safety and keeping food workers safe. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Over the last year, this project has provided the following opportunities for training and professional development: 1. I have developed and taught a new course for Spring 2020 (first in person, then moved online due to the pandemic): FSC 844, Risk Assessment of Foodborne Chemicals and Toxins. This covered didactics of the four stages of quantitative risk assessment, as well as lectures on food safety regulation in the US and around the world, the impact of climate change on food safety, and case studies of hazard assessments conducted by JECFA and IARC. 2. I have given a webinar for the Society for Risk Analysis (SRA) on food security issues surrounding the COVID-19 pandemic, particularly risks to food workers. 3. I have given two webinars on MSU's Closing Bell webinar series, speaking on COVID-19 risk in indoor spaces, and developments in COVID-19 treatments and the development of vaccine candidates. How have the results been disseminated to communities of interest?This past year has been especially productive in terms of publications and even distance classes and presentations during the pandemic. Our research team's results have been disseminated as folllows: 1. Publications: 7 peer-reviewed journal articles published, 2 more accepted / in press, 6 more under review; and 2 book chapters published. 2. Conference presentations in person at Society for Risk Analysis andMars-Wrigley Company, and webinars and podcasts for SRA, Closing Bell, the US Environmental Protection Agency, Bug Talk, and Carnegie Mellon University; on various aspects of food safety, particularly mycotoxins, burden of human disease, and effectiveness of interventions to improve food safety. What do you plan to do during the next reporting period to accomplish the goals?In the next year, my research team will continue our research on understanding the human health risk associated with exposure to mycotoxins, branching into impacts to our immune system. We will examine low-moisture food systems to reduce food contaminants in the US food supply, and will examine how new events of transgenic Bt corn and other biotech crops can help to counter some of the risks of aflatoxin in changing climate scenarios in the near future.

Impacts
What was accomplished under these goals? Over the past year, this Hatch grant has assisted us in furthering the stated objectives; branching out beyond foodborne mycotoxins to other foodborne toxins, as well as meeting current needs regarding the pandemic. Objective 1. Human health risk assessments of foodborne chemicals and toxins in the US and worldwide: We have examined occurrence of aflatoxin M1 nation by nation in milk and other dairy products, and have conducted an exposure assessement on a nation-by-nation basis based on AFM1 in their foodstuffs and intake rates of different dairy products. We have examined how the past 40 years of food safety risk assessmentin the US have affected US regulations regarding food safety, and developments in food safety technologies.We have evaluated the risk of cassava cyanide-induced cognitive impairment in children in Democratic Republic of the Congo, in terms of disability-adjusted life years. We have publisheda seminal chapter on foodborne chemicals and toxins in a toxicology textbook. Objective 2. Efficacy, cost-effectiveness, and feasibility of food contaminant control strategies in the US and worldwide: We have examined crop insurance claims to determine that where transgenic Bt corn is planted, there are significantly fewer aflatoxin-related insurance claims; controlling for climate and grower practices. We have determined the impact of lactic acid fermentation in reducing the mycotoxins aflatoxin and fumonisin in Nigerian maize intended for the porridge ogi.We have determined how technological advances in the last 25 years have reduced Fusarium head blight and deoxynivalenol in wheat. We have estimated the impact of the United Nations Codex Alimentarius Commission's deoxynivalenol guidelines on human health risk worldwide. We have evaluated the cost-effectiveness of a wetting method for cassava flour to remove the cyanide that causes konzo and children's cognitive impairment in Democratic Republic of the Congo. We have published a book chapter on the efficacy of the "dry chain" (keeping food as dry as possible from farm to fork) to reduce foodborne pathogens and mycotoxins. Objective 3. Estimation of climate-related changes to aflatoxin distribution in the US: We have developed models to predict how corn planting dates will change in the next 20 years, and how this affects how corn growth stages will coincide with vulnerabilities for Aspergillus flavus infection and aflatoxin contamination. We examine how this will affect the spread of aflatoxin problems in US corn in the near-term future.

Publications

• Type: Journal Articles Status: Published Year Published: 2019 Citation: Kim J, Mason NM, Snapp S, Wu F (2019). Does sustainable intensification of maize production enhance child nutrition? Evidence from rural Tanzania. Agricultural Economics 50:723-34.
• Type: Journal Articles Status: Published Year Published: 2020 Citation: Xia R, Schaafsma AW, Wu F, Hooker DC (2020). Economic impact of the improvements in Fusarium head blight and agronomic management on farm revenue and profit. World Mycotoxin Journal 13:423-39.
• Type: Journal Articles Status: Published Year Published: 2020 Citation: Greenberg M, Cox A, Bier V, Lambert J, Lowrie K, North W, Siegrist M, Wu F. (2020). Risk Analysis: Celebrating the Accomplishments and Embracing Ongoing Challenges. Risk Analysis. 24 June 2020. DOI: 10.1111/risa.13487.
• Type: Journal Articles Status: Published Year Published: 2020 Citation: Yu J, Hennessy DA, Wu F (2020). The impact of Bt corn on aflatoxin-related insurance claims in the United States. Scientific Reports 10:10046.
• Type: Journal Articles Status: Published Year Published: 2020 Citation: Malone T, Schaefer KA, Wu F (2020). The Razors Edge of Essential Labor in Food and Agriculture. Applied Economic Perspectives & Policy, doi:10.1002/aepp.13070.
• Type: Journal Articles Status: Awaiting Publication Year Published: 2020 Citation: Grace D, Wu F, Havelaar A (2020). Foodborne diseases from dairy products in developing countries: Review of causes and health and economic implications. Journal of Dairy Science, in press.
• Type: Journal Articles Status: Published Year Published: 2020 Citation: Xia R, Schaafsma AW, Wu F, Hooker DC (2020). The change in winter wheat response to deoxynivalenol and Fusarium Head Blight through technological and agronomic progress. Plant Disease, https://doi.org/10.1094/PDIS-06-20-1310-RE.
• Type: Journal Articles Status: Published Year Published: 2020 Citation: Ademola O, Saha Turna N, Liverpool-Tasie L, Obadina A, Wu F (2020). Food Processing and Mycotoxin Reduction in Maize-Based Products: Evidence from Lactic Acid Fermentation in Southwest Nigeria. Food Control, doi.org/10.1016/j.foodcont.2020.107620.
• Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Chen C, Wu F (2020). Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) colonization and infection among livestock workers and veterinarians: A systematic review and meta-analysis. Occupational and Environmental Medicine, accepted for publication.
• Type: Journal Articles Status: Under Review Year Published: 2020 Citation: Kim J, Mason-Wardell N, Mather D, Wu F (2020). The effects of the National Agricultural Input Voucher Scheme (NAIVS) on sustainable intensification of maize production in Tanzania. Journal of Agricultural Economics, revision stage.
• Type: Journal Articles Status: Under Review Year Published: 2020 Citation: Ye Z, Wu F, Hennessy DA (2020). A comprehensive welfare analysis of a glyphosate tax. Proceedings of the National Academy of Sciences, revision stage.
• Type: Journal Articles Status: Under Review Year Published: 2020 Citation: Chen C, Boivin M, Wu F (2020). Burden of disease of childrens cognitive impairment associated with cassava cyanide in Democratic Republic of the Congo. Trends in Food Science and Technology, under review.
• Type: Journal Articles Status: Under Review Year Published: 2020 Citation: Chen C, Kashala-Abotnes E, Banea Mayambu J-P, Mumba Ngoyi D, Tshala-Katumbay D, Mukeba D, Kunya M, Boivin MJ, Wu F (2020). Cost-effectiveness of a wetting method intervention to reduce cassava cyanide-related cognitive impairment in children. Nature Food, under review.
• Type: Journal Articles Status: Under Review Year Published: 2020 Citation: Wu F, Rodricks JV (2020). Forty years of food safety risk assessment: A history and analysis. Risk Analysis, under review.
• Type: Journal Articles Status: Under Review Year Published: 2020 Citation: Chen C, Frank K, Wang T, Wu F (2020). Global wheat trade and Codex Alimentarius Guidelines for Deoxynivalenol: A mycotoxin common in wheat. Nature Food, under review.
• Type: Book Chapters Status: Published Year Published: 2020 Citation: Bradford KJ, Dahal P, Van Asbrouck J, Kunusoth K, Bello P, Thompson J, Wu F. (2020). The Dry Chain: Reducing Postharvest Losses and Improving Food Safety in Humid Climates. In: Food Industry Wastes: Assessment and Recuperation of Commodities, 2nd Ed., Kosseva MR, Webb C, Eds., Elsevier, Amsterdam, The Netherlands, pp. 375-390.
• Type: Book Chapters Status: Published Year Published: 2020 Citation: Rodricks JV, Turnbull D, Chowdhury F, Wu F (2020). Food Constituents and Contaminants. In: Environmental Toxicants: Human Exposures and Their Health Effects, 4th Ed. Lippmann M and Leikauf GD, Eds., John Wiley & Sons, Hoboken, NJ, pp. 147-203.

Progress 10/01/18 to 09/30/19

Outputs
Target Audience:The target audience for this research includes: academia, food and agriculture industries, agricultural extension specialists in plant diseases that affect human health, and policymakers in the areas of food safety and agriculture. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?This project has supported one postdoctoral research fellow and three graduate students. The findings and methods relevant to this project have also been incorporated into my course FSC 844: Risk Assessment of Foodborne Chemicals and Toxins; and I have made presentations at multiple conferences and universities on the topics related to this research. How have the results been disseminated to communities of interest?We have published several papers (please see previous page);I have had several interviews and requests for "expert information" on food safety topics (please see previous page);and we have presented our work at multiple conferences including the Society of Toxicology, Society for Risk Analysis, Agricultural and Applied Economics Association, International Life Sciences Institute, Michigan Academy of Nutrition and Dietetics, Great Lakes Crop Summit, and multiple universities. What do you plan to do during the next reporting period to accomplish the goals?We will continue in our work with all of the Objectives listed above, including publishing our results from our research, and furthering the risk assessment of how aflatoxin may affect human and animal immunity - which would have national and international ramifications. This will be the core of our research thrust. We will also refine our aflatoxin-climate model with the inclusion of irrigation and its mitigating effect on fungal infection of corn.

Impacts
What was accomplished under these goals? Objective 1: We have conducted risk assessments on aflatoxin-related liver cancer in Bangladesh, fumonisin-related child stunting worldwide, and aflatoxin-related immunotoxicity examining multiple different immunological endpoints. Objective 2: We have examined the effectiveness of transgenic Bt corn, controlling for biocontrol use, climatic factors, and geography, in reducing aflatoxin in maize - and the economic impact of this in the United States. Objective 3: We have combined 17 climate prediction models to estimate the daily maximum temperatures during corn growing seasons throughout US states that plant corn, and estimated the risk of aflatoxin in these states as a result of near-term climatic conditions.

Publications

• Type: Journal Articles Status: Submitted Year Published: 2019 Citation: Xia R, Schaafsma AW, Wu F, Hooker DC (2019). Economic impact of the improvements in Fusarium head blight and agronomic management on farm revenue and profit. World Mycotoxin Journal, submitted.
• Type: Journal Articles Status: Submitted Year Published: 2019 Citation: Xia R, Schaafsma AW, Wu F, Hooker DC (2019). Winter wheat era response to deoxynivalenol accumulation, Fusarium head blight and agronomic performance. Plant Disease, submitted.
• Type: Journal Articles Status: Submitted Year Published: 2019 Citation: Chen C, Wu F (2019). Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) colonization and infection among livestock workers and veterinarians: A systematic review and meta-analysis. Bulletin of the World Health Organization, submitted.
• Type: Journal Articles Status: Published Year Published: 2019 Citation: Liverpool-Tasie L, Saha Turna N, Ademola O, Obadina A, Wu F (2019). The occurrence and co-occurrence of aflatoxin and fumonisin along the maize value chain in southwest Nigeria. Food and Chemical Toxicology 129:458-65.
• Type: Journal Articles Status: Published Year Published: 2019 Citation: Chen C, Saha Turna N, Wu F (2019). Risk assessment of dietary deoxynivalenol exposure in wheat products worldwide: Are new Codex DON guidelines adequately protective? Trends in Food Science and Technology 89:11-25.
• Type: Journal Articles Status: Published Year Published: 2019 Citation: Saha Turna N, Wu F (2019). Risk assessment of aflatoxins in Bangladesh: Is the general population at risk from dietary aflatoxin exposure? Food Additives and Contaminants 36:320-6.
• Type: Journal Articles Status: Published Year Published: 2018 Citation: Chen C, Riley RT, Wu F (2018). Dietary Fumonisin and Growth Impairment in Children and Animals: A Review. Comprehensive Reviews in Food Science and Food Safety 17:1448-64.

Progress 12/01/17 to 09/30/18

Outputs
Target Audience:The target audiences for this research are: academic researchers in agriculture, economics, food safety, and risk assessment; government officials in the United States and worldwide with a focus on food safety; farmers with an interest in strategies to reduce food contaminants; and industries and non-governmental organizations with a focus on food safety. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Training activities: During the 9 months of this project, I have supervised one postdoctoral research fellow and four PhD students, and also advise an additional fourPhD students in their research and studies related to food safety and security, toxicology, and risk assessment. I also taught the MSU course FSC 891: Food and Environmental Risk Assessment; covering many of the above-described topics. Professional development activities (workshops, conferences, seminars): I have given lectures in the following venues during this report period:Michigan Academy of Nutrition and Dietetics, University of Wisconsin Food Research Institute Symposium, University of California-BerkeleyInnovation in Agrifood Supply Chains Conference, and University of California-Davis World Food Center; on topics related to mycotoxins' health effects, mycotoxin control methods, and impacts of food safety regulation. How have the results been disseminated to communities of interest?In addition to the 1) peer-reviewed journal articles described in a previous page in this progress report, and 2) the university courses and 3) conference lectures described just above, I have also been 4) featured in five news articles about issues related to food safety and security during the past nine months: two in journals to the broad MSU community and alumni, and three online news sources (Yahoo! and SELF). What do you plan to do during the next reporting period to accomplish the goals?I will continue to carry out research and dissemination in the goals and objectives stated above.

Impacts
What was accomplished under these goals? Thanks to the support of this project, we have conducted research with important findings for US and global agriculture and food safety. Among our findings are the following: 1) We have determined that a mycotoxin, fumonisin (common in corn worldwide), is associated with childhood underweight, when controlling for nutritional, sanitary, and socioeconomic factors. 2) We have found that the greatest risk for livestock-acquired MRSA (methicillin-resistant Staphylococcus aureus) infection in humans is among swine farmers; followed by cattle farmers, veterinarians, and horse farmers. 3) We have found that genetically modified Bt corn substantially reduces the risk of the mycotoxinaflatoxin in US corn, as shown by crop insurance claims related to aflatoxin. 4) However, we predict that aflatoxin will become a much more significant problem in US corn in the next several decades, given changes in temperature and precipitation patterns. 5) We have identified cost-effective food drying technologies to substantially reduce the risk of mycotoxins in food. Our specific accomplishments under each project objective are as follows: 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. Major activities completed / experiments conducted: We have examined the impact of aflatoxin and fumonisin exposure on children's growth outcomes in Tanzania, controlling for nutritional, sanitary, and socioeconomic factors. We have reviewed the research conducted to date on fumonisin exposure and growth impairment in animals and children. We have assessed the risk of aflatoxin-induced liver cancer to the Bangladeshi population both before and after recent adoption of aflatoxin standards in that nation. We have conducted an exposure assessment and risk assessment of another mycotoxin, deoxynivalenol (DON), to human populations worldwide. Data collected: We have collected data on aflatoxin and fumonisin exposure in children in Tanzania, on studies linking fumonisin exposure to growth outcomes in animals and humans, on aflatoxin occurrence in foodstuffs in Bangladesh, on DON occurrence in both raw wheat and finished wheat products worldwide, and on wheat consumption patterns in different nations worldwide. Summary statistics and discssion of results: We have found that in our cohort of children in Tanzania, aflatoxin exposure was not associated with any growth outcomes after controlling for other influencing factors; but fumonisin was significantly associated with children's underweight after controlling for these factors. We have found that multiple studies since the 1980s have linked fumonisin exposure with growth impairment in animals, and in the last decade, increasing epidemiological evidence also links fumonisin exposure with growth impairment in infants and children. We have found that the new aflatoxin standards in Bangladesh are unlikely to significantly change the incidence of aflatoxin-related liver cancer in this nation's population. Finally, we have found that with respect to potential adverse human health effects from DON exposure, the Chinese population is likely to be at high risk. Key outcomes or other accomplishments realized: We have increased knowledge regarding both mycotoxin exposure and risks in multiple populations around the world. We have suggested methods to reduce mycotoxin exposure in at-risk populations. Ideally, in the future, these could lead to changed conditions for food safety and human health by awareness and adoption of means to reduce mycotoxin exposure. Objective 2: Evaluate the efficacy, cost-effectiveness, and feasibility of different mycotoxin control strategies in the US and in low-income settings worldwide. Major activities completed / experiments conducted: We have assessed the impact of transgenic Bt corn adoption on aflatoxin-related insurance claims among corn growersin the United States (controlling for climatic and geographical factors), to determine if Bt corn is in fact an effective strategy in reducing aflatoxin contamination of corn. We have also examined the potential for food drying mechanisms to improve food safety, including aflatoxin control, in cost-effective and technically feasible ways for low-resource populations. Data collected: We collected data from: the USDA Risk Management Agency on mycotoxin-related crop insurance claims, Kynetec Ltd. on Bt corn planting by crop reporting district, and NASA and NOAA for daily temperature and monthly Palmer Z indices (measure of drought). Summary statistics and discussion of results: For six states for the years spanning 2001-2011, we found that controlling for climatic and geographical variables, Bt corn planting is associated with fewer aflatoxin-related insurance claims. Also related to Objective 3 below: it appeared that drought conditions in June and July led to greater aflatoxin-related insurance claims, while wet conditions in September increased the same risk. Likewise, higher than normal temperatures in June and July increased aflatoxin risk. We also discussed the role of a "dry chain" (similar to a "cold chain") as a means of improving food safety by reducing microbial contaminants, including the fungi that produce mycotoxins. Key outcomes or other accomplishments realized: We have increased knowledge in the area of the secondary benefits of transgenic Bt corn, as well as identified a possible mechanism to reduce the risk of aflatoxin in corn. We hope that our work in this area as well as in the "dry chain" will eventually be more widely adopted to reduce the risk of aflatoxin and other food contaminants. 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. Major activities completed / experiments conducted: This work is ongoing. Our studies on the determinants of aflatoxin-related insurance claims among US corn growers (please see above) included examining daily max/min temperatures and monthly drought conditions during corn-growing months. We are now expanding to include NASA and NOAA predictions of future climate scenarios to determine the extent to which aflatoxin problems could either increase or decrease in different parts of the US in the decades to come. Data collected: 2001-2011NASA and NOAA data ondaily temperature and monthly Palmer Z indices (measure of drought). Ongoing: NASA and NOAA predictions for daily temperature and precipitation from 2031-2050. Summary statistics and discussion of results: Our findings from past aflatoxin-related insurance claims among corn growers from 2001-2011 reveal that aflatoxin risk is significantly higher when temperatures are unusually hot for June and July, when there are drought conditions (negative Palmer Z index) in June and July, and when there are wet conditions in September. Key outcomes and other accomplishments realized: We have increased knowledge about conditions under which aflatoxin is a likely risk in corn in different climatic scenarios. Ideally in the future, this will enable the corn industry (including seed companies, corn growers, grain elevators, and food companies) to prepare for potential aflatoxin problems in advance, by applying control methods at the proper times during corn growth stages to reduce aflatoxin risk.

Publications

• Type: Journal Articles Status: Submitted Year Published: 2019 Citation: Saha Turna N, Wu F (2018). Risk assessment of aflatoxins in Bangladesh: Is the general population at risk from dietary aflatoxin exposure? Food Additives and Contaminants, submitted.
• Type: Journal Articles Status: Submitted Year Published: 2019 Citation: Chen C, Wu F (2018). Methicillin-resistant Staphyloccus aureus (MRSA) colonization among livestock workers: A systematic review and meta-analysis. The Lancet Planetary Health, submitted.
• Type: Journal Articles Status: Submitted Year Published: 2019 Citation: Yu J, Hennessy D, Wu F (2018). The Impact of Bt Corn on Aflatoxin-Related Insurance Claims in the United States. Nature Biotechnology, submitted.
• Type: Journal Articles Status: Published Year Published: 2018 Citation: Chen C, Riley RT, Wu F (2018). Dietary Fumonisin and Growth Impairment in Children and Animals: A Review. Comprehensive Reviews in Food Science and Food Safety, DOI:10.1111/1541-4337.12392.
• Type: Journal Articles Status: Published Year Published: 2018 Citation: Chen C, Mitchell NJ, Gratz J, Houpt ER, Gong Y, Egner PA, Groopman JD, Riley RT, Showker JL, Svensen E, Mduma ER, Patil CL, Wu F. (2018). Exposure to aflatoxin and fumonisin in children at risk for growth impairment in rural Tanzania. Environment International 115:29-37.
• Type: Journal Articles Status: Published Year Published: 2018 Citation: Ogunade IM, Martinez-Tuppia C, Queiroz OCM, Jiang Y, Drouin P, Wu F, Vyas D, Adesogan AT (2018). Mycotoxins in Silage: Occurrence, Effects, Prevention and Mitigation. Journal of Dairy Science 101:4034-59.
• Type: Journal Articles Status: Published Year Published: 2018 Citation: Bradford KJ, Dahal P, Van Asbrouck J, Kunusoth K, Bello P, Thompson J, Wu F (2018). The Dry Chain: Reducing Postharvest Losses and Improving Food Safety in Humid Climates. Trends in Food Science & Technology 71:84-93.