Bt corn and cotton planting may benefit peanut growers by reducing aflatoxin risk.

Decades of studies have shown that Bt corn, by reducing insect damage, has lower levels of mycotoxins (fungal toxins), such as aflatoxin and fumonisin, than conventional corn. We used crop insurance data to infer that this benefit from Bt crops extends to reducing aflatoxin risk in peanuts: a non-Bt crop. In consequence, we suggest that any benefit-cost assessment of how transgenic Bt crops affect food safety should not be limited to assessing those crops alone; because the insect pest control offered by Bt crops affects the food safety profile of other crops grown nearby. Specifically, we found that higher Bt corn and Bt cotton planting rates in peanut-growing areas of the United States were associated with lower aflatoxin risk in peanuts as measured by aflatoxin-related insurance claims filed by peanut growers. Drought-related insurance claims were also lower: possibly due to Bt crops' suppression of insects that would otherwise feed on roots, rendering peanut plants more vulnerable to drought. These findings have implications for countries worldwide where policies allow Bt cotton but not Bt food crops to be grown: simply planting a Bt crop may reduce aflatoxin and drought stress in nearby food crops, resulting in a safer food supply through an inter-crop "halo effect."

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.

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.

"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.

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.

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.

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.

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.

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.

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.

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.

Dietary Fumonisin and Growth Impairment in Children and Animals: A Review.

Fumonisins are mycotoxins produced primarily by the fungi Fusarium verticillioides and F. proliferatum, which colonize maize in tropical, subtropical, and temperate climates worldwide. Fumonisin exposure is the highest in rural populations that consume large amounts of maize and maize products. Among them, infants and young children are the most vulnerable when they are weaned onto maize-based foods. Therefore, it is critical to understand the impact of fumonisin on children's health and growth. This review describes the evidence linking fumonisin exposure to child growth impairment. First, toxicological studies that attempt to elucidate the mechanism by which fumonisin may impair growth are discussed. Next, a description is given of candidate biomarkers for accurately capturing fumonisin exposure in humans. Potential human health effects of fumonisin exposure beyond growth impairment, including esophageal cancer and neural tube defects (NTDs), are briefly described. We review epidemiological studies that collectively show an increasing weight of evidence linking fumonisin exposure to growth impairment, particularly in world regions where young children consume maize-based weaning foods. Additionally, the evidence linking fumonisin exposure to growth impairment in plants and a variety of animal species are reviewed. Finally, we describe interventions to reduce fumonisin in parts of the world where dietary fumonisin exposure is high and is likely to predispose populations to increased health risk.

Data-driven methods for imputing national-level incidence in global burden of disease studies.

OBJECTIVE: To develop transparent and reproducible methods for imputing missing data on disease incidence at national-level for the year 2005. METHODS: We compared several models for imputing missing country-level incidence rates for two foodborne diseases - congenital toxoplasmosis and aflatoxin-related hepatocellular carcinoma. Missing values were assumed to be missing at random. Predictor variables were selected using least absolute shrinkage and selection operator regression. We compared the predictive performance of naive extrapolation approaches and Bayesian random and mixed-effects regression models. Leave-one-out cross-validation was used to evaluate model accuracy. FINDINGS: The predictive accuracy of the Bayesian mixed-effects models was significantly better than that of the naive extrapolation method for one of the two disease models. However, Bayesian mixed-effects models produced wider prediction intervals for both data sets. CONCLUSION: Several approaches are available for imputing missing data at national level. Strengths of a hierarchical regression approach for this type of task are the ability to derive estimates from other similar countries, transparency, computational efficiency and ease of interpretation. The inclusion of informative covariates may improve model performance, but results should be appraised carefully.

Ochratoxin A and human health risk: a review of the evidence.

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

Evaluating weight of evidence in the mystery of Balkan endemic nephropathy.

Balkan endemic nephropathy (BEN) is a chronic, progressive wasting disease of the kidneys, endemic in certain rural regions of the Balkan nations Croatia, Serbia, Bulgaria, and Romania. It is irreversible and ultimately fatal. Though this disease was first described in the 1950s, its causes have been a mystery and a source of much academic and clinical contention. Possible etiologic agents that have been explored include exposure to metals and metalloids, viruses and bacteria, and the dietary toxins aristolochic acid (AA) and ochratoxin A (OTA). AA is a toxin produced by weeds of the genus Aristolochia, common in Balkan wheat fields. Aristolochia seeds may intermingle with harvested grains and thus inadvertently enter human diets. OTA is a mycotoxin (fungal toxin) common in many foods, including cereal grains. In this study, we analyzed the weight of evidence for each of the suspected causes of BEN using the Bradford Hill criteria (BHC): nine conditions that determine weight of evidence for a causal relationship between an agent and a disease. Each agent postulated to cause BEN was evaluated using the nine criteria, and for each criterion was given a rating based on the strength of the association between exposure to the substance and BEN. From the overall available scientific evidence for each of these suspected risk factors, AA is the agent with the greatest weight of evidence in causing BEN. We describe other methods for testing causality from epidemiological studies, which support this conclusion of AA causing BEN.

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.

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.

Feed handling practices, aflatoxin awareness and children's milk consumption in the Sidama region of southern Ethiopia.

Consumption of milk is linked to improved nutrient intake and reduced risk of child malnutrition in low and middle-income countries. However, these benefits are contingent on the safety and quality of the milk. Milk consumption may alleviate the widespread risk of malnutrition in rural Ethiopia, but milk-borne contaminants may also compromise child health. We aimed to: i) identify the types of dairy feeds used, their storage conditions, and potential risk of aflatoxin contamination; ii) assess stakeholders' knowledge about aflatoxin contamination along the value chain; and iii) assess parental practices on feeding milk to infants and young children. This qualitative study was conducted in the Sidama region, southern Ethiopia. In-depth interviews (n = 12) and key-informant interviews (n = 18) were conducted with actors along the dairy value chain. Focus-group discussions were conducted with farmers (9FGD/n = 129) and child caregivers (9FGD/n = 122). Study participants were selected to represent a rural-urban gradient, as well as low- and high- dairy cow holdings. We found that while animal-feed processors and their distribution agents had relatively good knowledge about aflatoxin, farmers and retailers did not. Feed storage conditions were poor. Many respondents linked moldy feeds to animal health but not to human health. Farmers' feed choice was influenced by cost, seasonality, and herd size. Small-holding farmers had limited access to commercial feed. Children's consumption of milk was limited to skim milk, as butter was extracted and sold for income. The high cost of dairy products also led some parents to dilute skim milk with water before feeding children, compromising the nutritional value and safety of the milk. Our findings underscore the need to address the gaps in aflatoxin and food safety knowledge, improve storage conditions, and ensure the availability of quality feed to increase the sector's productivity, but most importantly to protect consumers' health and well-being, especially infants and young children.