Study protocol to assess aflatoxin M1 health risks versus benefits of dairy consumption in Ethiopian children: an epidemiological trial and risk-benefit analysis.

INTRODUCTION: In Sidama, Ethiopia, animal-source foods can be difficult to access. Milk has important nutrients for child growth, but carries the risk of aflatoxin M1 (AFM1) contamination. AFM1 is a metabolite of the mycotoxin aflatoxin B1 (AFB1) in dairy feed; cows secrete AFM1 in milk when their feed contains AFB1 produced by Aspergillus fungi in maize, nuts and oilseeds. It is unknown whether AFM1 compromises child growth and health. METHODS AND ANALYSIS: This protocol paper describes our study in Sidama to determine the impact of milk consumption and AFM1 on child growth in the first 18 months of life. We will collect baseline and end-line data on dairy production, socioeconomic and nutritional factors of 1000 dairy-owning households with children ages 6-18 months at baseline; and gather samples of milk and dairy feed and child anthropometrics. We will conduct phone interviews every 6 months to ascertain changes in practices or child health. Dairy feed will be tested for AFB1; milk for AFM1, pathogens and nutrients. Controlling for herd size, socioeconomic, nutritional and behavioural factors, we will determine the association between child anthropometrics and milk consumption, as well as AFM1 exposure. We will examine whether AFM1 exposure affects child growth in the first 18 months of life, and weigh the benefits and risks of milk consumption. ETHICS AND DISSEMINATION: The protocol is approved by the Institutional Review Boards of the Ethiopian Public Health Institute (EPHI-IRB-481-2022), Michigan State University (STUDY00007996) and International Food Policy Research Institute (DSGD-23-0102). Written informed consent will be obtained from all participants, who may withdraw from the study at any time. Confidentiality of collected data will be given high priority during each stage of data handling. The study's findings will be disseminated through stakeholder workshops, local and international conferences, journal articles and technical reports.

Children's cognitive impairment associated with cassava cyanide in Democratic Republic of the Congo: Burden of disease.

Worldwide, tens of millions of children rely on cassava as a dietary staple throughout their formative years of brain and behavioral development. Recently, it was discovered that cassava cyanide can impair children's neurocognitive development at relatively low exposures. We revisited the World Health Organization's foodborne disease burden estimate of cassava cyanide, focusing on the new health endpoint of children's cognitive impairment in Democratic Republic of the Congo (DRC). The loss of Intelligence Quotient (IQ) scores was used to measure the endpoint of cognitive impairment caused by cassava cyanide exposure, which was estimated based on the concentration-effect relationship between children's IQ scores and cyanide concentrations in flour. We estimated the burden of intellectual disability (ID) associated with cassava cyanide exposure in terms of disability-adjusted life years (DALYs). The median content of cyanide in cassava samples collected from DRC was 12.5 mg/kg, causing a median decrement to children's IQ of 2.37 points. The estimated number of children with ID associated with cassava cyanide exposure was 1,643 cases, although 1,567 of these cases (95%) were mild ID. The burden of cognitive impairment attributable to cassava cyanide in DRC alone was 13,862 DALYs per 100,000 children, or 3.01 million for all children under age 5. The results of the study, showing a significant burden of cassava cyanide-related cognitive impairment in children even at relatively low doses, can contribute to the implementation of cost-effective interventions to make cassava consumption safer for children in high-risk rural areas of DRC.

Health burden associated with tillage-related PM2.5 pollution in the United States, and mitigation strategies.

Exposure to airborne particulate matter of diameter less than 2.5 µm (PM2.5) is associated with cardiovascular diseases (CVD) and chronic obstructive pulmonary disease (COPD). In agriculture, the practice of tilling generates PM2.5 emissions that can jeopardize human health. This paper estimates the annual deaths and disability-adjusted life years (DALYs) from CVD and COPD attributable to PM2.5 emissions from corn, soybean, cotton, and wheat tillage in the contiguous United States. Primary PM2.5 from crop-tillage combination was calculated using values obtained from the Environmental Protection Agency's National Emissions Inventory, 2017, while deaths and DALYs estimates were calculated using data from the Institute of Health Metrics and Evaluation's global burden of risk factors study, the US decennial census, and the US Centers for Disease Control. We also propose and implement a conceptual framework for identifying the optimal subsidy upon accounting for health benefits arising from reducing conventional tillage, and we discuss strategies to achieve conservation tillage. Annual PM2.5 emissions from crop tillage is about 0.25 million tons. We estimate that approximately 1000 annual deaths and 22,000 DALYs from CVD, as well as 300 annual deaths and 7400 DALYs from COPD, were attributable to tillage-related PM2.5 emissions. Tillage related primary PM2.5 emissions contribute about 0.002 % of total CVD and COPD deaths in the United States, and its related health economic value loss is about 12.9 billion USD annually. About 350 annual deaths may be averted upon a shift from conventional to conservation tillage. Conservation tillage is generally adopted when the pecuniary and soil health benefits exceed those from adopting intensive tillage. Agricultural policies and on-farm measures that may help reduce intensive tillage, and the related PM2.5 emissions, include subsidies for adopting conservation tillage and carbon capture credits, use of herbicides and herbicide-tolerant crops, protecting herbicide-tolerance traits, planting cover crops, and use of windbreaks.

Effects of aflatoxin on the immune system: Evidence from human and mammalian animal research.

Shortly after its discovery in 1960, aflatoxin - a group of fungal toxins or mycotoxins produced by the fungi Aspergillus flavus and A. parasiticus in food crops such as maize, peanuts and tree nuts - was found to cause liver cancer in humans and multiple animal species. Hence, regulations on maximum allowable aflatoxin levels in food worldwide have focused on protecting humans from aflatoxin's carcinogenic effects. However, aflatoxin may also have non-carcinogenic health effects (e.g., immunotoxicity) that are particularly relevant today. Our current review highlights the growing evidence that aflatoxin exposure adversely affects immunity. Here, we comprehensively evaluated human and mammalian animal studies that link aflatoxin exposure with adverse effects on the immune system. We organized the review by organism as well as by the effects on adaptive and innate immune functions. There is abundant evidence that aflatoxin exhibits immunotoxicity, and therefore may compromise the ability of both humans and animals to resist infections. However, the reported effects of aflatoxin on certain specific immune biomarkers are inconsistent in the existing literature. The extent of the immunotoxic effects of aflatoxin must be clarified, so that the contribution of such immunotoxicity to the overall burden of aflatoxin-related diseases can be established.

Dietary exposure to cadmium from six common foods in the United States.

Recently, the United States (US) Food and Drug Administration (FDA) launched a Closer to Zero Action Plan to assess the risks of and develop action levels for certain heavy metals in food including cadmium (Cd). The problem of foodborne metal contamination has taken on new urgency, thanks in part to a 2021 US Congressional Report detailing high levels of metals found in infant food. Our risk assessment aids this FDA Action Plan by estimating the American population's Cd exposures in food, by age group and consumption patterns of certain high-risk foods; and by determining circumstances in which exposures exceed tolerable daily intakes developed by policymaking groups in the US and worldwide. We found that the age groups 6-24 months and 24-60 month old are the most highly exposed to Cd in common foodstuffs. American infants and young children of these age groups who regularly consumed rice, spinach, oats, barley, potatoes, and wheat had mean Cd exposures exceeding maximum tolerable intake level was set by the Agency for Toxic Substances and Disease Registry (ATSDR). We have identified age groups at highest potential risk, and therefore of interest for developing food safety policies to improve safety of commercial food for children.

Foodborne disease outbreaks in flour and flour-based food products from microbial pathogens in the United States, and their health economic burden.

The most comprehensive and inclusive estimates for the economic burden of foodborne illness yield values as high as $97.4 billion USD annually. However, broad incidence and cost estimates have limited use if they cannot be attributed to specific foods, for the purposes of food safety control. In this study, we estimated the economic burden of foodborne illnesses resulting from flour and flour-based food products in the United States from the years 2001 to 2021. The outbreak, illness burden, and health economic data are combined to generate these estimates. Our model combined outbreak data with published Centers for Disease Control and Prevention multipliers to estimate the annual number of illnesses associated with flour-borne pathogens. We then integrated illness severity data with an updated economic model that accounts for costs related to medical care, productivity loss, loss of life, along with the quality of life loss that entails pain and suffering. In total, 752 cases and 223 hospitalizations from flour-related illnesses were reported from 2001 to 2021, with an average of 37.6 cases of reported cases annually. However, the actual number of cases, accounting for underreporting and underdiagnosis, can be as high as 19,440 annually. Pathogens involved in these outbreaks are Salmonella, E. coli O157:H7, and E. coli O121. Our estimates suggest average annual economic losses, including healthy years of life lost, of $108 and $258 million using two alternative models.

"Modest doubt is called the beacon of the wise"-Incorporating uncertainty in risk analysis from Shakespeare to today.

"Modest doubt is call'd the beacon of the wise."-William Shakespeare, Troilus and Cressida. Although the character Hector warns his fellow Trojans with this line not to engage in war against the Greeks, Shakespeare's works are replete with characters who do not incorporate modest doubt, or any consideration of uncertainty, in their risk decisions. Perhaps Shakespeare was simply a keen observer of human nature. Although risk science has developed tremendously over the last five decades (and scientific inquiry over five centuries), the human mind still frequently defaults to conviction about certain beliefs, absent sufficient scientific evidence-which has effects not just on individual lives, but on policy decisions that affect many. This perspective provides background on the Shakespearean quote in its literary and historical context. Then, as this quote is the theme of the 2023 Society for Risk Analysis Annual Meeting, we describe how "modest doubt"-incorporating the notion of uncertainty into risk analysis for individual and policy decisions-is still the "beacon of the wise" today.

Mycotoxins were not associated with environmental enteropathy in a cohort of Tanzanian children.

Enteropathy is a pathophysiological condition characterized by decreased intestinal barrier function and absorption. Past studies have hypothesized that mycotoxins might impair children's growth by causing intestinal enteropathy, including interactions between mycotoxins and pathogens. We investigated the association of two mycotoxins, aflatoxin B1 (AFB1 ) and fumonisin B1 (FB1 ), independently and in conjunction with microbial pathogens, with fecal biomarkers of environmental enteropathy in children. As part of a larger MAL-ED study, 196 children were recruited in Haydom, Tanzania, and followed for the first 36 months of life. The gut inflammation biomarkers myeloperoxidase (MPO), neopterin (NEO), and alpha-1-antitrypsin (A1AT) were analyzed in stool samples at 24 months; with mean concentrations 5332.5 ng/L MPO, 807.2 nmol/L NEO, and 0.18 mg/g A1AT. Forty-eight children were measured for AFB1 -lys, with a mean of 5.30 (95% CI: 3.93-6.66) pg/mg albumin; and 87 were measured for FB1 , with a mean of 1.25 (95% CI: 0.72-1.76) ng/ml urine. Although the pathogens adenovirus and Campylobacter were associated with A1AT (p = 0.049) and NEO (p = 0.004), respectively, no association was observed between aflatoxin (MPO, p = 0.30; NEO, p = 0.08; A1AT, p = 0.24) or fumonisin (MPO, p = 0.38; NEO, p = 0.65; A1AT, p = 0.20) exposure and any gut inflammation biomarkers; nor were interactive effects found between mycotoxins and pathogens in contributing to intestinal enteropathy in this cohort. Although further studies are needed to confirm these results, it is possible that mycotoxins contribute to child growth impairment via mechanisms other than disrupting children's intestinal function.

Mycotoxin risks are lower in biotech corn.

Mycotoxins are food contaminants that occur when toxigenic fungi colonize crops. Unfortunately, corn, a major staple crop worldwide, is highly susceptible to mycotoxin contamination. Some mycotoxins, most notably aflatoxin, cause human cancer and other harmful effects such as immunotoxicity and growth impairment. Hence, many nations have set food-safety standards on mycotoxins. Aside from regulations, good agricultural and manufacturing practices lower mycotoxin risks. Agricultural biotechnology has made notable advances in reducing mycotoxins recently. While transgenic Bt corn has been known for years to reduce the mycotoxin fumonisin, new studies have shown its benefit in reducing aflatoxin as well. Other transgenic and RNA-interference corn hybrids target mycotoxin reduction specifically, and gene editing through clustered regularly interspaced short palindromic repeat systems has focused on preventing mycotoxin biosynthesis.

Aflatoxin M1 in milk does not contribute substantially to global liver cancer incidence.

BACKGROUND: For 60 y, it has been known that aflatoxin B1 (AFB1), a mycotoxin produced by Aspergillus fungi in certain food and feed crops, causes hepatocellular carcinoma (liver cancer; HCC) in humans. The annual global burden of AFB1-related HCC has been estimated. However, much less is known about the potential carcinogenic impact of a metabolite of AFB1 called aflatoxin M1 (AFM1), which is secreted in milk when dairy animals consume AFB1-contaminated feed. The cancer risk of AFM1 to humans from milk consumption has not yet been evaluated. OBJECTIVES: We sought to estimate the global risk of AFM1-related liver cancer through liquid milk consumption, accounting for possible synergies between AFM1 and chronic infection with hepatitis B virus (HBV) in increasing cancer risk. METHODS: We conducted a quantitative cancer risk assessment by analyzing extensive datasets of national population sizes, dairy consumption patterns, AFM1 concentrations in milk in 40 nations, and chronic HBV prevalence. Two separate cancer risk assessments were conducted: assuming a possible synergy between AFM1 and HBV in increasing cancer risk in a manner similar to that of AFB1 and HBV, and assuming no such synergy. RESULTS: If there is no synergy between AFM1 and HBV, AFM1 may contribute ∼0.001% of total annual HCC cases globally. If there is synergy between AFM1 and HBV infection, AFM1 may contribute ∼0.003% of all HCC cases worldwide. In each case, the total expected AFM1-attributable cancer cases are ∼13-32 worldwide. CONCLUSION: AFM1 exposure through liquid milk consumption does not substantially increase liver cancer risk in humans. Policymakers should consider this low risk against the nutritional benefits of milk consumption, particularly to children, in a current global situation of milk being discarded because of AFM1 concentrations exceeding regulatory standards.

Estimation of Tolerable Daily Intake (TDI) for Immunological Effects of Aflatoxin.

Aflatoxins are toxic chemicals produced by the fungi Aspergillus flavus and Aspergillus parasiticus. In warm climates, these fungi frequently contaminate crops such as maize, peanuts, tree nuts, and sunflower seeds. In many tropical and subtropical regions of the world, populations are coexposed to dietary aflatoxin and multiple infectious pathogens in food, water, and the environment. There is increasing evidence that aflatoxin compromises the immune system, which could increase infectious disease risk in vulnerable populations. Our aim was to conduct a dose-response assessment on a noncarcinogenic endpoint of aflatoxin: immunotoxicological effects. We sought to determine a noncarcinogenic tolerable daily intake (TDI) of aflatoxin, based on the existing data surrounding aflatoxin and biomarkers of immune suppression. To conduct the dose response assessment, mammalian studies were assessed for appropriateness of doses (relevant to potential human exposures) as well as goodness of data, and two appropriate mouse studies that examined decreases in leukocyte counts were selected to generate dose response curves. From these, we determined benchmark dose lower confidence limits (BMDL) as points of departure to estimate a range of TDIs for aflatoxin-related immune impairment: 0.017-0.082 µg/kg bw/day. As aflatoxin is a genotoxic carcinogen, and regulations concerning its presence in food have largely focused on its carcinogenic effects, international risk assessment bodies such as the Joint Expert Committee on Food Additives (JECFA) have never established a TDI for aflatoxin. Our work highlights the importance of the noncarcinogenic effects of aflatoxin that may have broader public health impacts, to inform regulatory standard-setting.

Environmental and economic concerns surrounding restrictions on glyphosate use in corn.

Since the commercialization of transgenic glyphosate-tolerant (GT) crops in the mid-1990s, glyphosate has become the dominant herbicide to control weeds in corn, soybean, and other crops in the United States and elsewhere. However, recent public concerns over its potential carcinogenicity in humans have generated calls for glyphosate-restricting policies. Should a policy to restrict glyphosate use, such as a glyphosate tax, be implemented? The decision involves two types of tradeoffs: human health and environmental (HH-E) impacts versus market economic impacts, and the use of glyphosate versus alternative herbicides, where the alternatives potentially have more serious adverse HH-E effects. Accounting for farmers' weed management choices, we provide empirical evaluation of the HH-E welfare and market economic welfare effects of a glyphosate use restriction policy on US corn production. Under a glyphosate tax, farmers would substitute glyphosate for a combination of other herbicides. Should a 10% glyphosate tax be imposed, then the most conservative welfare estimate is a net HH-E welfare gain with a monetized value of US$6 million per annum but also a net market economic loss of US$98 million per annum in the United States, which translates into a net loss in social welfare. This result of overall welfare loss is robust to a wide range of tax rates considered, from 10 to 50%, and to multiple scenarios of glyphosate's HH-E effects, which are the primary sources of uncertainties about glyphosate's effects.

Cost-effectiveness of a wetting method intervention to reduce cassava cyanide-related cognitive impairment in children.

Cassava cyanide-related neurocognitive impairment may persist for years in Central African children who rely on cassava as a dietary staple. In the Democratic Republic of the Congo, a cassava processing method, the 'wetting method', reduced cyanide in cassava, prevented konzo, and proved a cost-effective intervention to improve children's cognitive development. Scaling up use of the wetting method may help prevent neurocognitive impairment in millions of at-risk children in sub-Saharan Africa.

The Change in Winter Wheat Response to Deoxynivalenol and Fusarium Head Blight Through Technological and Agronomic Progress.

Fusarium head blight (FHB) in wheat causes yield loss, quality reduction, and mycotoxin contamination in temperate wheat production areas worldwide. The objective of this study was to quantify the progress of agronomic and FHB management strategies over the past two decades in FHB suppression and agronomic performance of winter wheat in environments favorable for FHB. Field experiments were conducted in environments typical of FHB epidemics to compare common agronomic and FHB management practices used in the 1996 era compared with those used in 2016. The experiments included a comparison of three different nitrogen (N) fertilizer application rates and six old (1996-era) and new (modern-era) winter wheat cultivars representing combinations of susceptibility and era to FHB, with and without a fungicide applied at flowering (pydiflumetofen + propiconazole). To mimic environments favorable for infection (similar to 1996 in Ontario, Canada), plots were challenged at 50% anthesis with F. graminearum macroconidia suspension followed by mist irrigation. The modern management strategy of using moderately resistant cultivars, a fungicide applied at flowering, and a high rate of N fertilizer reduced total deoxynivalenol by 67%, reduced Fusarium-damaged kernels by 49%, reduced FHB index by 86%, increased grain test weight by 11%, and increased grain yield by 31% compared with the standard management practice of seeding highly susceptible cultivars with no fungicide and a lower rate of N fertilizer recommended in the 1996 era. This study enabled a published economic assessment of the return on investment for the improvements in cultivars, fungicide, and N fertilizer applications since 1996.

Author Correction: The Impact of Bt Corn on Aflatoxin-Related Insurance Claims in the United States.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Forty Years of Food Safety Risk Assessment: A History and Analysis.

Before the founding of the Society for Risk Analysis (SRA) in 1980, food safety in the United States had long been a concern, but there was a lack of systematic methods to assess food-related risks. In 1906, the U.S. Congress passed, and President Roosevelt signed, the Pure Food and Drug Act and the Meat Inspection Act to regulate food safety at the federal level. This Act followed the publication of multiple reports of food contamination, culminating in Upton Sinclair's novel The Jungle, which highlighted food and worker abuses in the meatpacking industry. Later in the 20th century, important developments in agricultural and food technology greatly increased food production. But chemical exposures from agricultural and other practices resulted in major amendments to federal food laws, including the Delaney Clause, aimed specifically at cancer-causing chemicals. Later in the 20th century, when quantitative risk assessment methods were given greater scientific status in a seminal National Research Council report, food safety risk assessment became more systematized. Additionally, in these last 40 years, food safety research has resulted in increased understanding of a range of health effects from foodborne chemicals, and technological developments have improved U.S. food safety from farm to fork by offering new ways to manage risks. We discuss the history of food safety and the role risk analysis has played in its evolution, starting from over a century ago, but focusing on the last 40 years. While we focus on chemical risk assessment in the U.S., we also discuss microbial risk assessment and international food safety.

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) colonisation and infection among livestock workers and veterinarians: a systematic review and meta-analysis.

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is an increasing public health concern worldwide. The objective of this study was to calculate a summary odds ratio (OR) of livestock-associated MRSA colonisation and infection in humans, and to determine specific risk factors in livestock production contributing to MRSA colonisation. METHODS: We screened PubMed and Embase for studies published from 2005 to 2019 inclusive, reporting livestock-associated (LA)-MRSA colonisation and infection among livestock workers/veterinarians, their families, and community members not regularly exposed to livestock. The primary outcome of interest was the OR of LA-MRSA colonisation comparing exposed and control groups. Quality was assessed according to the Newcastle-Ottawa quality assessment scale. A meta-analysis using a random-effects model was conducted to calculate a pooled OR. The heterogeneity in the meta-analysis was assessed using the I² method, and publication bias was evaluated using funnel plots. RESULTS: A total of 3490 studies were identified by the search, with 37 studies including 53 matched exposed-control groups and 14 038 participants eligible for the meta-analysis. The pooled OR for LA-MRSA among livestock workers and veterinarians is 9.80 (95% CI 6.89 to 13.95; p=0.000; I2 =73.4), with no significant publication bias (Egger's p=0.66). The OR for swine workers was highest at 15.41 (95% CI 9.24 to 25.69), followed by cattle workers (11.62, 95% CI 4.60 to 29.36), veterinarians (7.63, 95% CI 3.10 to 18.74), horse workers (7.45, 95% CI 2.39 to 23.25), livestock workers (5.86, 95% CI 1.14 to 30.16), poultry workers (5.70, 95% CI 1.70 19.11), and industrial slaughterhouse workers (4.69, 95% CI 1.10 to 20.0). CONCLUSIONS: Livestock workers, particularly swine farmers, are at significantly higher risk for LA-MRSA colonisation and subsequent infection. These results support the need for preventive practices to reduce LA-MRSA risk among those who handle and treat livestock. TRIAL REGISTRATION NUMBER: CRD42019120403.

Risk Analysis: Celebrating the Accomplishments and Embracing Ongoing Challenges.

As part of the celebration of the 40th anniversary of the Society for Risk Analysis and Risk Analysis: An International Journal, this essay reviews the 10 most important accomplishments of risk analysis from 1980 to 2010, outlines major accomplishments in three major categories from 2011 to 2019, discusses how editors circulate authors' accomplishments, and proposes 10 major risk-related challenges for 2020-2030. Authors conclude that the next decade will severely test the field of risk analysis.

The Impact of Bt Corn on Aflatoxin-Related Insurance Claims in the United States.

Previous field studies have reached no collective consensus on whether Bt corn, the most commonly planted transgenic crop worldwide, has significantly lower aflatoxin levels than non-Bt isolines. Aflatoxin, a mycotoxin contaminating corn and other commodities, causes liver cancer in humans and can pose severe economic losses to farmers. We found that from 2001-2016, a significant inverse correlation existed between Bt corn planting and aflatoxin-related insurance claims in the United States, when controlling for temperature and drought. Estimated benefits of aflatoxin reduction resulting from Bt corn planting are about $120 million to $167 million per year over 16 states on average. These results suggest that Bt corn use is an important strategy in reducing aflatoxin risk, with corresponding economic benefits. If the same principles hold true in other world regions, then Bt corn hybrids adapted to diverse agronomic regions may have a role in reducing aflatoxin in areas prone to high aflatoxin contamination, and where corn is a dietary staple.