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The goal of this study was to assess a cadmium (Cd) physiologically based pharmacokinetic (PBPK) model to evaluate Cd toxicological reference values (e.g. reference dose, tolerable intake, minimum risk level) adapted to the U.S. population. We reviewed and evaluated previously published Cd PBPK models and developed further adaptations to the 1978 Kjellström and Nordberg (KN) model. Specifically, we propose adaptations with updated U.S.-specific bodyweight, kidney weight and creatinine excretion models by using NHANES data as well as a stochastic PBPK model that provides credible intervals of uncertainty around mean populational estimates. We provide our model review and adaptations as well as present estimates from the newly adapted models using observed U.S. urinary Cd values as a function of gender and age and given dietary exposure as evaluated from NHANES/WWEIA and U.S. Total Diet Study data. Results show all newly adapted models provide acceptable mean estimates of urinary Cd in the U.S. The stochastic model provides credible intervals to further inform regulatory decision making. Validation of the estimated K-Cd concentration values was not possible as data for a representative population was not available. We developed a web-based tool implementing these models and other potential adaptations to facilitate PBPK model estimate comparisons.

The serovars ofSalmonella entericadisplay dramatic differences in pathogenesis and host preferences. GroupingSalmonellaisolates and serovars by their public health risk can provide better Salmonellacontrol targets along the food chain. We collated a curated set of 12,337S. entericaisolate genomes from human, beef, and bovine sources in the US. After annotating a virulence gene catalog for each isolate, we used unsupervised random forest methods to estimate the proximity (similarity) between isolates based upon the genomic presentation of putative virulence traits We then grouped isolates (virulence clusters) using hierarchical clustering (Ward’s method), used non-parametric bootstrapping to assess cluster stability, and externally validated the virulence clusters against epidemiological virulence measures from FoodNet, the National Outbreak Reporting System (NORS), and US federal sampling of beef products. We identified five stable virulence clusters ofS. entericaserovars. Cluster 1 serovars yielded an annual incidence rate of domestically acquired sporadic cases roughly one and a half times higher than the other four clusters combined. Compared to other clusters, cluster 1 also had a higher proportion of infections leading to hospitalization and was implicated in more foodborne and beef-associated outbreaks, despite being isolated at a similar frequency from beef products as other clusters. We also identified subpopulations within 11 serovars. Remarkably, we foundS. Infantis andS. Typhimurium subpopulations that significantly differed in genome length and clinical case presentation. Further, we found that the presence of the pESI plasmid accounted for the genome length differences between theS. Infantis subpopulations. Our results demonstrate thatS. entericastrains with the highest incidence of human infections share a common virulence repertoire. This work could be used in combination with foodborne surveillance information to best target serovars of public health concern.

The objective of this study was to leverage quantitative risk assessment to investigate possible root cause(s) of foodborne illness outbreaks related to Shiga toxin-producing Escherichia coli O157:H7 (STEC O157) infections in leafy greens in the United States. To this end, we developed the FDA leafy green quantitative risk assessment epidemic curve prediction model (FDA-LG QRA-EC) that simulated the lettuce supply chain. The model was used to predict the number of reported illnesses and the epidemic curve associated with lettuce contaminated with STEC O157 for a wide range of scenarios representing various contamination conditions and facility processing/sanitation practices. Model predictions were generated for fresh-cut and whole lettuce, quantifying the differing impacts of facility processing and home preparation on predicted illnesses. Our model revealed that the timespan (i.e., number of days with at least one reported illness) and the peak (i.e., day with the most predicted number of reported illnesses) of the epidemic curve of a STEC O157-lettuce outbreak were not strongly influenced by facility processing/sanitation practices and were indications of contamination pattern among incoming lettuce batches received by the facility or distribution center. Through comparisons with observed number of illnesses from recent STEC O157-lettuce outbreaks, the model identified contamination conditions on incoming lettuce heads that could result in an outbreak of similar size, which can be used to narrow down potential root cause hypotheses.

We developed an association model to estimate the risk of femoral neck low bone mass and osteoporosis from exposure to cadmium for women and men aged 50-79 in the U.S, as a function of the urinary cadmium (U-Cd) levels. We analyzed data from the NHANES 2005-2014 surveys and evaluated the relationship between U-Cd and femoral neck bone mineral density (BMD) using univariate and multivariate regression models with a combination of NHANES cycle, gender, age, smoking, race/ethnicity, height, body weight, body mass index, lean body mass, diabetes, kidney disease, physical activity, menopausal status, hormone replacement therapy, urinary lead, and prednisone intake as confounding variables. The regression coefficient between U-Cd and femoral neck BMD obtained with the best multivariate regression was used to develop an association model that can estimate the additional risk of low bone mass or osteoporosis in the population given a certain level of U-Cd. Results showed a linear relationship between U-Cd and BMD, conditional to body weight, where individuals with higher U-Cd had decreased BMD values. Our results do not support the hypothesis of a threshold for the effect of Cd on bone. Our model estimates that exposure to Cd results in an increase of 0.51 percentage points (CI95% 0.00, 0.92) of the population diagnosed with osteoporosis, compared to a theoretical absence of exposure. We estimate that 16% (CI95%: 0.00, 40%) of osteoporosis cases in the U.S. 50-79 aged population are a result of Cd exposure. This study presents the first continuous model estimating low bone mass and osteoporosis risk in the U.S. population given actual or potential changes in U-Cd levels. Our model will provide information to inform FDA's Closer to Zero initiative goal to reduce exposure to toxic elements.

Reduction of foodborne illness caused by norovirus (NoV) continues to be a focus for the food safety community. Using a previously published quantitative risk assessment model, we evaluated more than 60 scenarios examining the impact of implementation of and compliance with risk management strategies identified in the U.S. Food and Drug Administration Food Code for (a) surface cleaning and sanitizing, (b) hand hygiene, (c) exclusion, or (d) restriction of ill employees. Implementation of and compliance with hand hygiene and ill food employee exclusion strategies had the largest impact on the predicted number of highly contaminated food servings and associated consumer illnesses. In scenarios in which gloves were always worn and hand washing compliance was 90%, the model estimated reductions in the number of highly contaminated food servings and ill consumers to 39 and 43% of baseline estimates (i.e., typical practice), respectively. Reductions were smaller when gloves were never worn. Hand washing compliance after using the restroom strongly impacted predicted numbers of highly contaminated servings and consumer illnesses. Ten percent compliance with removing or excluding ill food employees was predicted to increase the number of highly contaminated food servings and ill consumers to 221 and 213% of baseline estimates, respectively. Ninety-four percent compliance with exclusion of ill food employees was predicted to decrease these numbers to 69 and 71% of baseline estimates, respectively. Surface cleaning in food establishments had a relatively small impact on these measures. Restriction of food employees (removed from contact with food and food contact equipment and utensils) was not effective for reducing NoV illness unless this restriction included additional provisions. The results from this study can help risk managers prioritize mitigation strategies and their implementation for controlling the transmission of NoV and subsequent consumer foodborne illness.

Listeria monocytogenes is a foodborne pathogen that disproportionally affects pregnant females, older adults, and immunocompromised individuals. Using U.S. Foodborne Diseases Active Surveillance Network (FoodNet) surveillance data, we examined listeriosis incidence rates and rate ratios (RRs) by age, sex, race/ethnicity, and pregnancy status across three periods from 2008 to 2016, as recent incidence trends in U.S. subgroups had not been evaluated. The invasive listeriosis annual incidence rate per 100,000 for 2008–2016 was 0.28 cases among the general population (excluding pregnant females), and 3.73 cases among pregnant females. For adults ≥70 years, the annual incidence rate per 100,000 was 1.33 cases. No significant change in estimated listeriosis incidence was found over the 2008–2016 period, except for a small, but significantly lower pregnancy-associated rate in 2011–2013 when compared with 2008–2010. Among the nonpregnancy-associated cases, RRs increased with age from 0.43 (95% confidence interval: 0.25–0.73) for 0- to 14-year olds to 44.9 (33.5–60.0) for ≥85-year olds, compared with 15- to 44-year olds. Males had an incidence of 1.28 (1.12–1.45) times that of females. Compared with non-Hispanic whites, the incidence was 1.57 (1.18–1.20) times higher among non-Hispanic Asians, 1.49 (1.22–1.83) among non-Hispanic blacks, and 1.73 (1.15–2.62) among Hispanics. Among females of childbearing age, non-Hispanic Asian females had 2.72 (1.51–4.89) and Hispanic females 3.13 (2.12–4.89) times higher incidence than non-Hispanic whites. We observed a higher percentage of deaths among older patient groups compared with 15- to 44-year olds. This study is the first characterizing higher RRs for listeriosis in the United States among non-Hispanic blacks and Asians compared with non-Hispanic whites. This information for public health risk managers may spur further research to understand if differences in listeriosis rates relate to differences in consumption patterns of foods with higher contamination levels, food handling practices, comorbidities, immunodeficiencies, health care access, or other factors.

Human norovirus (NoV) is the leading cause of foodborne illness in the United States and Canada. Bivalve molluscan shellfish is one commodity commonly identified as being a vector of NoV. Bivalve molluscan shellfish are grown in waters that may be affected by contamination events, tend to bioaccumulate viruses, and are frequently eaten raw. In an effort to better assess the elements that contribute to potential risk of NoV infection and illness from consumption of bivalve molluscan shellfish, the U.S. Department of Health and Human Services/Food and Drug Administration (FDA), Health Canada (HC), the Canadian Food Inspection Agency (CFIA), and Environment and Climate Change Canada (ECCC) collaborated to conduct a quantitative risk assessment for NoV in bivalve molluscan shellfish, notably oysters. This study describes the model and scenarios developed and results obtained to assess the risk of NoV infection and illness from consumption of raw oysters harvested from a quasi-steady-state situation. Among the many factors that influence the risk of NoV illness for raw oyster consumers, the concentrations of NoV in the influent (raw, untreated) and effluent (treated) of wastewater treatment plants (WWTP) were identified to be the most important. Thus, mitigation and control strategies that limit the influence from human waste (WWTP outfalls) in oyster growing areas have a major influence on the risk of illness from consumption of those oysters.

In food safety, process pathway risk assessments usually estimate the risk of illness from a single hazard and a single food and can inform food safety decisions and consumer advice. To evaluate the health impact of a potential change in diet, we need to understand not only the risk posed by the considered hazard and food but also the risk posed by the substitution food and other potential hazards. We developed a framework to provide decision-makers with a multi-faceted evaluation of the impact of dietary shifts on risk of illness. Our case study explored exposure to inorganic arsenic (iAs) and aflatoxins through consumption of infant cereals and the risk of developing lung, bladder and liver cancer over a lifetime. The estimated additional Disability-Adjusted Life Year (DALY) in the U.S. from exposure to iAs and aflatoxin based on available contamination and consumption patterns of infant rice and oat cereal is 4,921 (CI 90% 414; 9,071). If all infant cereal consumers shift intake (maintaining equivalent serving size and frequency) to only consuming infant rice cereal, the predicted DALY increases to 6,942 (CI 90% 326; 12,931). If all infant cereal consumers shift intake to only consuming infant oat cereal, the predicted DALY decreases to 1,513 (CI 90% 312; 3,356). Changes in contaminant concentrations or percent consumers, that could occur in the future, also significantly impact the predicted risk. Uncertainty in these risk predictions is primarily driven by the dose-response models. A risk-risk analysis framework provides decision-makers with a nuanced understanding of the public health impact of dietary changes and can be applied to other food safety and nutrition questions.

Variability is the law of life, and as no two faces are the same, so no two bodies are alike, and no two individuals react alike and behave alike under the abnormal conditions which we know as disease. While it is recommended to consider and evaluate variability and uncertainty separately, these two concepts are nevertheless frequently misunderstood or misused. A useful way to think about sources of variability is to consider these four broad categories: Variability is observed in each component of risk assessments for biological and chemical hazards in food. The variability in serving size or frequency of consumption is also an element that explains the exposure assessment variability. These approaches include useful elements to consider when constructing an appropriate generic uncertainty analysis framework. The result of a risk assessment that consider uncertainty is a single value integrating variability. In practice, some resources exist to conduct second-order Monte-Carlo simulations.

We developed a probabilistic mathematical model for the postharvest processing of leafy greens focusing on Escherichia coli O157:H7 contamination of fresh-cut romaine lettuce as the case study. Our model can (i) support the investigation of cross-contamination scenarios, and (ii) evaluate and compare different risk mitigation options. We used an agent-based modeling framework to predict the pathogen prevalence and levels in bags of fresh-cut lettuce and quantify spread of E. coli O157:H7 from contaminated lettuce to surface areas of processing equipment. Using an unbalanced factorial design, we were able to propagate combinations of random values assigned to model inputs through different processing steps and ranked statistically significant inputs with respect to their impacts on selected model outputs. Results indicated that whether contamination originated on incoming lettuce heads or on the surface areas of processing equipment, pathogen prevalence among bags of fresh-cut lettuce and batches was most significantly impacted by the level of free chlorine in the flume tank and frequency of replacing the wash water inside the tank. Pathogen levels in bags of fresh-cut lettuce were most significantly influenced by the initial levels of contamination on incoming lettuce heads or surface areas of processing equipment. The influence of surface contamination on pathogen prevalence or levels in fresh-cut bags depended on the location of that surface relative to the flume tank. This study demonstrates that developing a flexible yet mathematically rigorous modeling tool, a "virtual laboratory," can provide valuable insights into the effectiveness of individual and combined risk mitigation options.

Listeriosis is an invasive illness typically caused by the ingestion of foods contaminated with Listeria monocytogenes. In 2015, an outbreak of listeriosis was linked to ice cream products produced on a specific production line at Facility X. The United States Food and Drug Administration (FDA) obtained samples representing several lots of three products manufactured on that line from May 2014 through January 2015. Two of these products, A and B, while not linked to any reported illnesses, were analyzed to determine the frequency of contamination and the contamination level for risk assessment and dose-response analyses. These enumerations were performed utilizing a Most Probable Number (MPN) method, with a lower detection limit of 0.03 MPN/g, on 344 samples of Product A and 95 samples of Product B. Ten lots of Product A were analyzed and 77% of the samples tested were found to be positive for L. monocytogenes. Five lots of Product B were analyzed and 46% of the tested samples were found to be positive. Additionally, the level of contamination of positive Product B samples was always less than 1 MPN/g. The contamination levels of both products, overall, were low with median values of 0.1 MPN/g and 0.02 MPN/g for Products A and B, respectively. A majority of Product A samples (52%) were contaminated at levels of less than 1 MPN/g and only one sample was above 100 MPN/g. Whole genome sequencing (WGS) of L. monocytogenes isolated from ice cream samples produced in the line suggested minor strain differences related to product type, possibly due to differences in the food matrices and/or differences in the manufacturing equipment. Overall, the data showed a consistent low level of contamination in products produced from a single production line over a nine month period.

Listeria monocytogenes is an important cause of foodborne illness hospitalization, fetal loss, and death in the United States. Listeriosis incidence rate varies significantly among population subgroups with pregnant women, older persons, and the Hispanic population having increased relative risks compared with the other subpopulations. Using estimated rates of listeriosis per subpopulation based on FoodNet data from 2004 to 2009, we evaluate the expected number of cases and incidence rates of listeriosis in the US population and the pregnant women subpopulation as the demographic composition changes over time with respect to ethnicity, pregnancy status, and age distribution. If the incidence rate per subpopulation is held constant, the overall US population listeriosis incidence rate would increase from 0.25 per 100,000 (95% confidence interval [CI]: 0.19–0.34) in 2010 to 0.28 (95% CI: 0.22–0.38) in 2020 and 0.32 (95% CI: 0.25–0.43) in 2030, because of the changes in the population structure. Similarly, the pregnancy-associated incidence rate is expected to increase from 4.0 per 100,000 pregnant women (95% CI: 2.5–6.5) in 2010 to 4.1 (95% CI: 2.6–6.7) in 2020 and 4.4 (95% CI: 2.7–7.2) in 2030 as the proportion of Hispanic pregnant women increases. We further estimate that a reduction of 12% in the exposure of the US population to L. monocytogenes would be needed to maintain a constant incidence rate from 2010 to 2020 (current trend), assuming infectivity (strain virulence distribution and individual susceptibility) is unchanged. To reduce the overall US population incidence rate by one-third (Healthy People 2020 goal) would require a reduction in exposure (or infectivity) to L. monocytogenes of 48% over the same time period. Reduction/elimination in exposure of pregnant and Hispanic subpopulations alone could not meet this target. This information may be useful in setting public health targets, developing risk management options, and in interpreting trends in the public health burden of foodborne listeriosis in the United States.

A quantitative risk assessment was conducted to assess the risk of human salmonellosis acquired from consumption of pecans in the United States. The model considered the potential for Salmonella survival, growth, and recontamination of pecans from the sheller to the consumer, including steps such as immersion in water, drying, conditioning, cracking, partitioning, and storage. Five theoretical microbial reduction treatment levels (1 to 5 log CFU) were modeled. Data from the 2010 to 2013 surveys by the National Pecan Shellers Association were used for initial prevalence and contamination levels. The impacts of atypical situations in the pecan production system were also evaluated. Higher initial contamination levels, recontamination during processing, and a delay in drying postconditioning were the modeled atypical situations. The baseline model predicted a mean risk of salmonellosis in the United States from consumption of in-shell and shelled pecans processed by cold conditioning with no microbial reduction treatment and no further home cooking as 1 case per 775,193 servings (95% confidence interval [CI]: 1 case per 1,915,709 to 178,253 servings). This predicted risk per serving was estimated as a mean of 529 cases of salmonellosis per year (95% CI: 213 to 2,295 cases). Hot conditioning for shelled pecans and microbial reduction treatment of both shelled and in-shell pecans had a significant impact on the predicted mean risk of illness. Assuming 77% of the shelled pecans sold at retail (i.e., 80% of the retail supply) received hot conditioning, the mean estimated salmonellosis cases per year from consumption of in-shell and shelled pecans uncooked at home was 203 (95% CI: 81 to 882 cases) if no additional microbial reduction treatment were applied. The predicted risk of illness per serving was higher for all atypical situations modeled compared with the baseline model, and delay in drying had the greatest impact on risk.

A multiyear interagency Listeria monocytogenes Market Basket Survey was undertaken for selected refrigerated ready-to-eat foods purchased at retail in four FoodNet sites in the United States. Food samples from 16 food categories in six broad groups (seafood, produce, dairy, meat, eggs, and combination foods) were collected weekly at large national chain supermarkets and independent grocery stores in California, Maryland, Connecticut, and Georgia for 100 weeks between December 2010 and March 2013. Of the 27,389 total samples, 116 samples tested positive by the BAX PCR system for L. monocytogenes , and the pathogen was isolated and confirmed for 102 samples. Among the 16 food categories, the proportion of positive samples (i.e., without considering clustering effects) based on recovery of a viable isolate of L. monocytogenes ranged from 0.00% (95% confidence interval: 0.00, 0.18) for the category of soft-ripened and semisoft cheese to 1.07% (0.63, 1.68) for raw cut vegetables. Among the 571 samples that tested positive for Listeria-like organisms, the proportion of positive samples ranged from 0.79% (0.45, 1.28) for soft-ripened and semisoft cheese to 4.76% (2.80, 7.51) for fresh crab meat or sushi. Across all 16 categories, L. monocytogenes contamination was significantly associated with the four states (P < 0.05) but not with the packaging location (prepackaged by the manufacturer versus made and/or packaged in the store), the type of store (national chain versus independent), or the season. Among the 102 samples positive for L. monocytogenes , levels ranged from

We developed a quantitative risk assessment model using a discrete event framework to quantify and study the risk associated with norovirus transmission to consumers through food contaminated by infected food employees in a retail food setting. This study focused on the impact of ill food workers experiencing symptoms of diarrhea and vomiting and potential control measures for the transmission of norovirus to foods. The model examined the behavior of food employees regarding exclusion from work while ill and after symptom resolution and preventive measures limiting food contamination during preparation. The mean numbers of infected customers estimated for 21 scenarios were compared to the estimate for a baseline scenario representing current practices. Results show that prevention strategies examined could not prevent norovirus transmission to food when a symptomatic employee was present in the food establishment. Compliance with exclusion from work of symptomatic food employees is thus critical, with an estimated range of 75–226% of the baseline mean for full to no compliance, respectively. Results also suggest that efficient handwashing, handwashing frequency associated with gloving compliance, and elimination of contact between hands, faucets, and door handles in restrooms reduced the mean number of infected customers to 58%, 62%, and 75% of the baseline, respectively. This study provides quantitative data to evaluate the relative efficacy of policy and practices at retail to reduce norovirus illnesses and provides new insights into the interactions and interplay of prevention strategies and compliance in reducing transmission of foodborne norovirus.

Nuts have been identified as a vector for salmonellosis. The objective of this project was to estimate the prevalence and contamination level of Salmonella in raw tree nuts (cashews, pecans, hazelnuts, macadamia nuts, pine nuts, and walnuts) at retail markets in the United States. A total of 3,656 samples of six types of tree nuts were collected from different types of retail stores and markets nationwide between October 2014 and October 2015. These samples were analyzed using a modified version of the Salmonella culture method from the U.S. Food and Drug Administration's Bacteriological Analytical Manual. Of the 3,656 samples collected and tested, 32 were culturally confirmed as containing Salmonella. These isolates represented 25 serotypes. Salmonella was not detected in pecans and in-shell hazelnuts. Salmonella prevalence estimates (and 95% confidence intervals) in cashews, shelled hazelnuts, pine nuts, walnuts, and macadamia nuts were 0.55% [0.15, 1.40], 0.35% [0.04, 1.20], 0.48% [0.10, 1.40], 1.20% [0.53, 2.40], and 4.20% [2.40, 6.90], respectively. The rates of Salmonella isolation from major or big chain supermarkets, small chain supermarkets, discount, variety, or drug stores, and online were 0.64% [0.38, 1.00], 1.60% [0.80, 2.90], 0.00% [0.00, 2.40], and 13.64% [2.90, 35.00], respectively (Cochran-Mantel-Haenszel test: P = 0.02). The rates of Salmonella isolation for conventional and organic nuts were not significantly different. Of the samples containing Salmonella, 60.7% had levels less than 0.003 most probable number (MPN)/g. The highest contamination level observed was 0.092 MPN/g. The prevalence and levels of Salmonella in these tree nut samples were comparable to those previously reported for similar foods.

According to the U.S. Food and Drug Administration's (FDA's) rule on "Prevention of Salmonella Enteritidis in Shell Eggs during Production, Storage, and Transportation," shell eggs intended for human consumption are required to be held or transported at or below 45°F (7.2°C) ambient temperature beginning 36 h after time of lay. Meanwhile, eggs in hatcheries are typically stored at a temperature of 65°F (18.3°C). Although most of those eggs are directed to incubators for hatching, excess eggs have the potential to be diverted for human consumption as egg products through the "breaker" market if these eggs are refrigerated in accordance with FDA's requirement. Combining risk assessment models developed by the U.S. Department of Agriculture's Food Safety and Inspection Service for shell eggs and for egg products, we quantified and compared Salmonella Enteritidis levels in eggs held at 65°F versus 45°F, Salmonella Enteritidis levels in the resulting egg products, and the risk of human salmonellosis from consumption of those egg products. For eggs stored 5 days at 65°F (following 36 h at 75°F [23.9°C] in the layer house), the mean level of Salmonella Enteritidis contamination is 30-fold higher than for eggs stored at 45°F. These increased levels of contamination lead to a 47-fold increase in the risk of salmonellosis from consumption of egg products made from these eggs, with some variation in the public health risk on the basis of the egg product type (e.g., whole egg versus whole egg with added sugar). Assuming that 7% of the liquid egg product supply originates from eggs stored at 65°F versus 45°F, this study estimates an additional burden of 3,562 cases of salmonellosis per year in the United States. A nominal range uncertainty analysis suggests that the relative increase in the risk linked to the storage of eggs at higher temperature estimated in this study is robust to the uncertainty surrounding the model parameters. The diversion of eggs from broiler production to human consumption under the current storage practices of 65°F (versus 45°F) would present a substantive overall increase in the risk of salmonellosis. HIGHLIGHTS

OBJECTIVES: We developed a framework to provide decision makers with a multi-faceted evaluation of the impact of dietary shifts on risk of illness in the U.S. population. METHODS: We collected representative data on prevalence and concentration of inorganic arsenic and aflatoxin in infant rice and oat cereal. Exposure to these contaminants through consumption and risk of illness from cancer were assessed per consumer based on data from the National Health and Nutrition Examination Survey and published dose-response and related data. The expected number of additional cases of illness and disability-adjusted life years (DALYs) for the U.S. population were estimated. The public health impact of shifts in consumption from one product to the other considered marginal and joint consumption and characterized uncertainty arising from estimates of contaminant concentrations, bioavailability and dose-response models. Monte Carlo simulations were developed in R and a Shiny app was created. RESULTS: Based on current consumption of infant rice and oat cereal, the estimated additional DALY for the total US population from inorganic arsenic and aflatoxin is 4,600 (CI 90% [370; 8,400]). If all consumers shift their consumption (maintaining equivalent servings) to only infant rice or only infant oat cereal, the estimated DALY increases to 1.4 and decreases to 0.4 relative to the baseline, respectively. Changes in contaminant concentrations or % consumers also significantly impact risk. Uncertainty in risk estimates is primarily driven by the dose-response models for this case study. The case study showcases applicability of the framework for a wide range of food safety and nutrition questions. Results support previous advice on varying grain intake in children. CONCLUSIONS: The current risk-risk framework can provide decision makers with a nuanced understanding of the impact of consumption shifts on public health and reveal parameters that drive predicted changes in public health. The Shiny app provides a real-time visualization tool to facilitate understanding and allow direct query by decision makers. FUNDING SOURCES: This work was carried out under official duties or contract with U.S. FDA.

A precise and accurate method for enumeration of low level of Listeria monocytogenes in foods is critical to a variety of studies. In this study, paired comparison of most probable number (MPN) and direct plating enumeration of L. monocytogenes was conducted on a total of 1730 outbreak-associated ice cream samples that were naturally contaminated with low level of L. monocytogenes. MPN was performed on all 1730 samples. Direct plating was performed on all samples using the RAPID'L.mono (RLM) agar (1600 samples) and agar Listeria Ottaviani and Agosti (ALOA; 130 samples). Probabilistic analysis with Bayesian inference model was used to compare paired direct plating and MPN estimates of L. monocytogenes in ice cream samples because assumptions implicit in ordinary least squares (OLS) linear regression analyses were not met for such a comparison. The probabilistic analysis revealed good agreement between the MPN and direct plating estimates, and this agreement showed that the MPN schemes and direct plating schemes using ALOA or RLM evaluated in the present study were suitable for enumerating low levels of L. monocytogenes in these ice cream samples. The statistical analysis further revealed that OLS linear regression analyses of direct plating and MPN data did introduce bias that incorrectly characterized systematic differences between estimates from the two methods.

Listeriosis can occur in susceptible populations when products with low-level contamination are distributed widely., The relationship between the number of ingested Listeria monocytogenes cells in food and the likelihood of developing listeriosis is not well understood. Data from an outbreak of listeriosis linked to milkshakes made from ice cream produced in 1 factory showed that contaminated products were distributed widely to the public without any reported cases, except for 4 cases of severe illness in persons who were highly susceptible. The ingestion of high doses of L. monocytogenes by these patients infected through milkshakes was unlikely if possible additional contamination associated with the preparation of the milkshake is ruled out. This outbreak illustrated that the vast majority of the population did not become ill after ingesting a low level of L. monocytogenes but raises the question of listeriosis cases in highly susceptible persons after distribution of low-level contaminated products that did not support the growth of this pathogen.

We assessed the risk of human salmonellosis from consumption of shelled walnuts in the United States and the impact of 0- to 5-log reduction treatments for Salmonella during processing. We established a baseline model with Salmonella contamination data from 2010 to 2013 surveys of walnuts from California operations to estimate baseline prevalence and levels of Salmonella during preshelling storage and typical walnut processing stages, considered U.S. consumption data, and applied an adapted dose-response model from the Food and Agriculture Organization and the World Health Organization to evaluate risk of illness per serving and per year. Our baseline model predicted 1 case of salmonellosis per 100 million servings (95% confidence interval [CI], 1 case per 3 million to 1 case per 2 billion servings) of walnuts untreated during processing and uncooked by consumers, resulting in an estimated 6 cases of salmonellosis per year (95% CI,1 to 278 cases) in the United States. A minimum 3-log reduction treatment for Salmonella during processing of walnuts eaten alone or as an uncooked ingredient resulted in a mean risk of1 case per year. We modeled the impact on risk per serving of three atypical situations in which the Salmonella levels were increased by 0.5 to 1.5 log CFU per unit pretreatment during processing at the float tank or during preshelling storage or posttreatment during partitioning into consumer packages. No change in risk was associated with the small increase in levels of Salmonella at the float tank, whereas an increase in risk was estimated for each of the other two atypical events. In a fourth scenario, we estimated the risk per serving associated with consumption of walnuts with Salmonella prevalence and levels from a 2014 to 2015 U.S. retail survey. Risk per serving estimates were two orders of magnitude larger than those of the baseline model without treatment. Further research is needed to determine whether this finding reflects variability in Salmonella contamination across the supply or a rare event affecting a portion of the supply.

Seven animal drugs [penicillin G (PENG), sulfadimethoxine (SDMX), oxytetracycline (OTET), erythromycin (ERY), ketoprofen (KETO), thiabendazole (THIA), and ivermectin (IVR)] were used to evaluate the drug distribution between milk fat and skim milk fractions of cow milk. More than 90% of the radioactivity was distributed into the skim milk fraction for ERY, KETO, OTET, PENG, and SDMX, approximately 80% for THIA, and 13% for IVR. The distribution of drug between milk fat and skim milk fractions was significantly correlated to the drug's lipophilicity (partition coefficient, log P, or distribution coefficient, log D, which includes ionization). Data were fit with linear mixed effects models; the best fit was obtained within this data set with log D versus observed drug distribution ratios. These candidate empirical models serve for assisting to predict the distribution and concentration of these drugs in a variety of milk and milk products.

Human norovirus (NoV) is the leading cause of foodborne illness in the United States and Canada. Wastewater treatment plant (WWTP) effluents impacting bivalve mollusk-growing areas are potential sources of NoV contamination. We have developed a meta-analysis that evaluates WWTP influent concentrations and log 10 reductions of NoV genotype I (NoV GI; in numbers of genome copies per liter [gc/liter]), NoV genotype II (NoV GII; in gc/liter), and male-specific coliphage (MSC; in number of PFU per liter), a proposed viral surrogate for NoV. The meta-analysis included relevant data (2,943 measurements) reported in the scientific literature through September 2013 and previously unpublished surveillance data from the United States and Canada. Model results indicated that the mean WWTP influent concentration of NoV GII (3.9 log 10 gc/liter; 95% credible interval [CI], 3.5, 4.3 log 10 gc/liter) is larger than the value for NoV GI (1.5 log 10 gc/liter; 95% CI, 0.4, 2.4 log 10 gc/liter), with large variations occurring from one WWTP to another. For WWTPs with mechanical systems and chlorine disinfection, mean log 10 reductions were −2.4 log 10 gc/liter (95% CI, −3.9, −1.1 log 10 gc/liter) for NoV GI, −2.7 log 10 gc/liter (95% CI, −3.6, −1.9 log 10 gc/liter) for NoV GII, and −2.9 log 10 PFU per liter (95% CI, −3.4, −2.4 log 10 PFU per liter) for MSCs. Comparable values for WWTPs with lagoon systems and chlorine disinfection were −1.4 log 10 gc/liter (95% CI, −3.3, 0.5 log 10 gc/liter) for NoV GI, −1.7 log 10 gc/liter (95% CI, −3.1, −0.3 log 10 gc/liter) for NoV GII, and −3.6 log 10 PFU per liter (95% CI, −4.8, −2.4 PFU per liter) for MSCs. Within WWTPs, correlations exist between mean NoV GI and NoV GII influent concentrations and between the mean log 10 reduction in NoV GII and the mean log 10 reduction in MSCs.

We developed a risk assessment of human salmonellosis associated with consumption of alfalfa sprouts in the United States to evaluate the public health impact of applying treatments to seeds (0–5‐log10 reduction in Salmonella) and testing spent irrigation water (SIW) during production. The risk model considered variability and uncertainty in Salmonella contamination in seeds, Salmonella growth and spread during sprout production, sprout consumption, and Salmonella dose response. Based on an estimated prevalence of 2.35% for 6.8 kg seed batches and without interventions, the model predicted 76,600 (95% confidence interval (CI) 15,400–248,000) cases/year. Risk reduction (by 5‐ to 7‐fold) predicted from a 1‐log10 seed treatment alone was comparable to SIW testing alone, and each additional 1‐log10 seed treatment was predicted to provide a greater risk reduction than SIW testing. A 3‐log10 or a 5‐log10 seed treatment reduced the predicted cases/year to 139 (95% CI 33–448) or 1.4 (95% CI

This study examined the inactivation of human norovirus (HuNoV) GI.1 and GII.4 by chlorine under conditions mimicking sewage treatment. Using a porcine gastric mucin-magnetic bead (PGM-MB) assay, no statistically significant loss in HuNoV binding (inactivation) was observed for secondary effluent treatments of ≤25 ppm total chlorine; for both strains, 50 and 100 ppm treatments resulted in ≤0.8-log 10 unit and ≥3.9-log 10 unit reductions, respectively. Treatments of 10, 25, 50, and 100 ppm chlorine inactivated 0.31, 1.35, >5, and >5 log 10 units, respectively, of the norovirus indicator MS2 bacteriophage. Evaluation of treatment time indicated that the vast majority of MS2 and HuNoV inactivation occurred in the first 5 min for 0.2-μm-filtered, prechlorinated secondary effluent. Free chlorine measurements of secondary effluent seeded with MS2 and HuNoV demonstrated substantial oxidative burdens. With 25, 50, and 100 ppm treatments, free chlorine levels after 5 min of exposure ranged from 0.21 to 0.58 ppm, from 0.28 to 16.7 ppm, and from 11.6 to 53 ppm, respectively. At chlorine treatment levels of >50 ppm, statistically significant differences were observed between reductions for PGM-MB-bound HuNoV (potentially infectious) particles and those for unbound (noninfectious) HuNoV particles or total norovirus particles. While results suggested that MS2 and HuNoV (measured as PGM-MB binding) behave similarly, although not identically, both have limited susceptibility to chlorine treatments of ≤25 ppm total chlorine. Since sewage treatment is performed at ≤25 ppm total chlorine, targeting free chlorine levels of 0.5 to 1.0 ppm, these results suggest that traditional chlorine-based sewage treatment does not inactivate HuNoV efficiently. IMPORTANCE HuNoV is ubiquitous in sewage. A receptor binding assay was used to assess inactivation of HuNoV by chlorine-based sewage treatment, given that the virus cannot be routinely propagated in vitro . Results reported here indicate that chlorine treatment of sewage is not effective for inactivating HuNoV unless chlorine levels are above those routinely used for sewage treatment.

The U.S. Food and Drug Administration conducted a survey to evaluate Salmonella prevalence and aerobic plate counts in packaged (dried) spices offered for sale at retail establishments in the United States. The study included 7,250 retail samples of 11 spice types that were collected during November 2013 to September 2014 and October 2014 to March 2015. No Salmonella-positive samples (based on analysis of 125 g) were found among retail samples of cumin seed (whole or ground), sesame seed (whole, not roasted or toasted, and not black), and white pepper (ground or cracked), for prevalence estimates of 0.00% with 95% Clopper and Pearson's confidence intervals of 0.00 to 0.67%, 0.00 to 0.70%, and 0.00 to 0.63%, respectively. Salmonella prevalence estimates (confidence intervals) for the other eight spice types were 0.19% (0.0048 to 1.1%) for basil leaf (whole, ground, crushed, or flakes), 0.24% (0.049 to 0.69%) for black pepper (whole, ground, or cracked), 0.56% (0.11 to 1.6%) for coriander seed (ground), 0.19% (0.0049 to 1.1%) for curry powder (ground mixture of spices), 0.49% (0.10 to 1.4%) for dehydrated garlic (powder, granules, or flakes), 0.15% (0.0038 to 0.83%) for oregano leaf (whole, ground, crushed, or flakes), 0.25% (0.03 to 0.88%) for paprika (ground or cracked), and 0.64% (0.17 to 1.6%) for red pepper (hot red pepper, e.g., chili, cayenne; ground, cracked, crushed, or flakes). Salmonella isolates were serotyped, and genomes were sequenced. Samples of these same 11 spice types were also examined from shipments of imported spices offered for entry to the United States from 1 October 2011 to 30 September 2015. Salmonella prevalence estimates (based on analysis of two 375-g composite samples) for shipments of imported spices were 1.7 to 18%. The Salmonella prevalence estimates for spices offered for sale at retail establishments for all of the spice types except dehydrated garlic and basil were significantly lower than estimates for shipments of imported spice offered for entry.

The impact of temperature, water activity (aw), and nut composition on Salmonella survival on tree nuts has not been thoroughly examined. The aim of this study was to determine the effect of temperature, aw, and nut composition on the survival of Salmonella on tree nuts and develop predictive models. Pecans, hazelnuts, and pine nuts were chosen based on differences in their typical fat content. Nuts were inoculated with a cocktail of five Salmonella serotypes (11 log CFU/mL) and then were dried and stored at 4, 10, and 25°C at 0.41 ± 0.06 and 0.60 ± 0.05 aw for 1 year. Ten-gram quantities were removed at different intervals up to 364 days to test for surviving Salmonella populations (plating on selective and nonselective media) and aw. Experiments were carried out in triplicate. Salmonella populations were relatively stable over a year at 4 and 10°C at both aw levels with

The presence of Salmonella on almonds continues to result in product-related outbreaks and recalls in the United States. In this study, the impact of microbial reduction treatment levels (1 to 5 log CFU) on the risk of human salmonellosis from the consumption of almond kernels in the United States was evaluated. An exposure model, including major steps in almond processing, was used to estimate prevalence and levels of contamination of Salmonella on almonds at the point of consumption. A Salmonella dose-response model and consumption data for almonds in the United States were used to assess risk of illness per serving and per year, quantifying variability and uncertainty separately. A 3-log reduction treatment resulted in a predicted mean risk of illness of two cases per year for almonds consumed as a core product not cooked at home (95% confidence interval [CI], one to four cases), one case per year for almonds consumed as an ingredient not cooked at home (95% CI, one to two cases), and less than one case per year for almonds consumed as an ingredient cooked at home (95% CI, 7 × 10-7 to 3 × 10-6 cases). A minimum 4-log reduction treatment resulted in an estimated mean risk of illness below one case per year in the United States. This study also includes an assessment of the risk of human salmonellosis as a result of an exceptional situation, which results in higher risk estimates compared with the baseline model. The exceptional situations modeled posttreatment resulted in estimates of mean risk that were not significantly affected by treatment level. Sensitivity analysis results showed initial Salmonella contamination level to be the factor with the most impact on risk per serving estimates, given a certain treatment level. The risk assessment also includes a simulation of the events that occurred in 2001. Treatment levels with a minimum 4-log microbial reduction would have been sufficient to prevent the outbreak cases. The uncertainty range in the estimates indicates that additional information is needed to make more precise predictions of this specific outbreak event.

Contaminated produce has been identified as the cause of several listeriosis outbreaks in recent years. Listeria monocytogenes is widely distributed in the environment and complete prevention of produce contamination is therefore challenging. Mitigation options that reduce contamination on produce are valuable, especially for produce commodities that are commonly consumed fresh or minimally processed. We performed a systematic review and meta-analysis of the available peer-reviewed literature to evaluate the efficacy of liquid fresh produce wash compounds in reducing produce contamination with L. monocytogenes, and derive quantitative estimates of treatment efficacy for a variety of common liquid fresh produce wash compounds. Treatment efficacy differed considerably across produce commodities, with liquid fresh produce wash compounds generally showing considerably greater efficacy for some tested commodities than for other commodities. Most but not all of the evaluated liquid fresh produce wash compounds were significantly more effective in reducing L. monocytogenes contamination than water alone, with mean reductions in L. monocytogenes levels ranging from less than 1 log10 cfu to more than 5 log10 cfu. Liquid fresh produce wash compounds are therefore a possible tool for reducing contamination with L. monocytogenes, for certain produce commodities.

In the U.S., chicken-breeder farms that supply hatcheries typically store and transport eggs intended for broiler production at a temperature of 18.3 °C (65 °F). However, in case of surplus, some of these eggs may be diverted to human consumption. According to the U.S. Food and Drug Administration's ‘Egg Safety Final Rule,’ shell eggs intended for human consumption are required to be held or transported at or below 7.2 °C (45 °F) ambient temperature beginning 36 h after time of lay. We adapted a risk assessment model developed by the U.S. Department of Agriculture's Food Safety Inspection Service, to quantify human exposure to Salmonella Enteritidis and the risk of human salmonellosis if eggs are held and transported at 18.3 °C for up to 5.5 days after time of lay, as has been observed when hatchery eggs are diverted to human consumption, rather than held and transported at 7.2 °C within 36 h after time of lay. Storage at 18.3 °C leads to considerable bacterial growth in internally contaminated eggs. The model predicted that more than 10% of internally contaminated eggs would remain contaminated after in-shell pasteurization resulting in a 5-log 10 reduction, and that some bacteria would survive after home-cooking. The model predicted that, alternatively, eggs stored at 7.2 °C after lay would have limited bacterial growth prior to pasteurization, and Salmonella would be very unlikely to be present after pasteurization. The predicted risk of salmonellosis from the consumption of eggs held and transported at 18.3 °C and subsequently diverted to human consumption is 25 times higher than the risk when eggs are held and transported at 7.2 °C.

Evaluations of Listeria monocytogenes dose-response relationships are crucially important for risk assessment and risk management, but are complicated by considerable variability across population subgroups and L. monocytogenes strains. Despite difficulties associated with the collection of adequate data from outbreak investigations or sporadic cases, the limitations of currently available animal models, and the inability to conduct human volunteer studies, some of the available data now allow refinements of the well-established exponential L. monocytogenes dose response to more adequately represent extremely susceptible population subgroups and highly virulent L. monocytogenes strains. Here, a model incorporating adjustments for variability in L. monocytogenes strain virulence and host susceptibility was derived for 11 population subgroups with similar underlying comorbidities using data from multiple sources, including human surveillance and food survey data. In light of the unique inherent properties of L. monocytogenes dose response, a lognormal-Poisson dose-response model was chosen, and proved able to reconcile dose-response relationships developed based on surveillance data with outbreak data. This model was compared to a classical beta-Poisson dose-response model, which was insufficiently flexible for modeling the specific case of L. monocytogenes dose-response relationships, especially in outbreak situations. Overall, the modeling results suggest that most listeriosis cases are linked to the ingestion of food contaminated with medium to high concentrations of L. monocytogenes. While additional data are needed to refine the derived model and to better characterize and quantify the variability in L. monocytogenes strain virulence and individual host susceptibility, the framework derived here represents a promising approach to more adequately characterize the risk of listeriosis in highly susceptible population subgroups.

Twenty five minerals and trace elements were determined by flame atomic absorption spectrometry and inductively coupled plasma mass spectrometry in 64 pooled foods prepared “as consumed”, representing 96.5% of the total diet in Yaounde, Cameroon. High element contents (in mg kg −1 ) of some food samples are highlighted. “Dried spices for local sauce” (raw/toasted) highly contained calcium (7720), iron (143), magnesium (1970), potassium (20,100), copper (12.6), manganese (109), aluminium (120), and lead (14.3). “Dried and smoked fish and shrimps” (boiled) contained high levels of calcium (21,200), potassium (7300), zinc (43.6), aluminium (27.8), and arsenic (1.14). “Garden huckleberry and amaranth” (boiled/washed fresh leaves) contained high levels of calcium (3580), manganese (15.9) and barium (19.4). “Squash beans and sesame” (boiled) provided magnesium (1240), and zinc (29.5). “Shelled groundnut” (soaked/grilled/boiled) contained high levels of magnesium (1040), zinc (31.5), and copper (8.32). Selenium was found only in fish as mackerel (0.467) and sea bass (0.450). No food product exceeded the maximum levels set for lead, mercury and cadmium by the current European regulation. These results will be used for dietary exposure and health risk assessment.

In response to increased concerns about spice safety, the United States Food and Drug Administration (FDA) initiated research to characterize the prevalence and levels of Salmonella in imported spices. 299 imported dried capsicum shipments and 233 imported sesame seed shipments offered for entry to the United States were sampled. Observed Salmonella shipment prevalence was 3.3% (1500 g examined; 95% CI 1.6-6.1%) for capsicum and 9.9% (1500 g; 95% Confidence Interval (CI) 6.3-14%) for sesame seed. Within shipment contamination was not inconsistent with a Poisson distribution. Shipment mean Salmonella level estimates among contaminated shipments ranged from 6 × 10(-4) to 0.09 (capsicum) or 6 × 10(-4) to 0.04 (sesame seed) MPN/g. A gamma-Poisson model provided the best fit to observed data for both imported shipments of capsicum and imported shipments of sesame seed sampled in this study among the six parametric models considered. Shipment mean levels of Salmonella vary widely between shipments; many contaminated shipments contain low levels of contamination. Examination of sampling plan efficacy for identifying contaminated spice shipments from these distributions indicates that sample size of spice examined is critical. Sampling protocols examining 25 g samples are predicted to be able to identify a small fraction of contaminated shipments of imported capsicum or sesame seeds.