Lack of genotoxicity potential and safety assessment of 4-(2-hydroxyethyl) morpholine present as an impurity in pharmaceuticals and nutritional supplements.

4-(2-Hydroxyethyl) morpholine (HEM) is widely used as a building block of macromolecules in the manufacture of pharmaceuticals and dietary supplements and could remain as an impurity in the finished products. An evaluation of HEM was conducted to identify endpoints that could be used to determine the point-of-departure (POD) for use in assessing the potential risk from exposure to HEM. No oral repeated dose toxicological studies of appropriate duration were found for HEM. Therefore, suitable analogue(s) were identified. Although oral repeated dose studies were available for the analogues, the studies were not of sufficient duration for use in the assignment of a POD for risk evaluation. Accordingly, the Threshold of Toxicological Concern (TTC) approach, which proposes that a de minimis value can be derived to qualitatively assess risk, was considered for HEM. To determine the appropriate TTC approach (genotoxic or non-genotoxic), the genotoxicity of HEM and its analogues were evaluated. The weight of the evidence indicated that HEM, and the appropriate analogues, are not genotoxic. Considering the chemical structure of HEM, the non-genotoxic Cramer class III TTC value of 1.5 µg/kg bw/day was determined to be appropriate for use in safety assessment of HEM as an impurity in products intended for human consumption.

Beverage Consumption Patterns among U.S. Adolescents and Adults from a New 24-h Beverage Recall Survey Compared to the National Health and Nutrition Examination Survey (NHANES) 2017-2018.

Beverages are major dietary components of the United States (U.S.) population. Understanding the current consumption pattern of beverages is an important element in supporting healthy diets. Our objective was to assess the validity of the 24-h beverage consumption recall data collected in 2021 through a self-administered online questionnaire (referred to as the American Beverage Association-Brandscapes Worldwide survey, ABA-BSW) by comparing it to the 24-h dietary recall data collected in the 2017-2018 National Health and Nutrition Examination Survey (NHANES). Summary statistics on the reported consumption amounts and consumption occasions (COs) of 13 beverage types (e.g., bottled water, carbonated soft drinks (CSD), tea, and others) by participants aged 13-64 years were compared between ABA-BSW (n = 20,553) and NHANES (n = 4437). The average daily consumption amount among consumers of all 13 beverage types combined was higher in ABA-BSW than in NHANES (1903 mL/day vs. 1704 mL/day). Within each beverage type, the average daily consumption amounts among consumers were generally lower in ABA-BSW except for CSD, plant-based drinks, and still juices and fruit-flavored drinks. Compared to NHANES, ABA-BSW participants reported consuming a wider variety of beverage groups, a higher number of COs per day, and lower consumption amounts within a given CO. Overall, beverage consumption patterns observed in ABA-BSW and NHANES were generally similar, supporting the design and implementation of the former survey. Further, the ABA-BSW data provide additional information on the within-day temporal beverage consumption patterns among adolescents and adults in the U.S. Differences in the observed consumption patterns between the surveys may be the result of various factors, including the survey implementation method, a consumption pattern shift between the survey time periods, beverage type availability, and impact of the COVID-19 pandemic on dietary patterns.

Potassium chloride-based replacers: modeling effects on sodium and potassium intakes of the US population with cross-sectional data from NHANES 2015-2016 and 2009-2010.

BACKGROUND: Sodium intake in the USA exceeds recommendations. The replacement of added sodium chloride (NaCl) with potassium chloride (KCl) provides a potential strategy to reduce sodium intake. OBJECTIVE: The purpose of this study was to quantitatively estimate changes in intakes of sodium and potassium by the US population assuming use of potassium-based NaCl replacers in top dietary sodium sources. METHODS: Data collected in the What We Eat in America (WWEIA) component of the 2015-2016 and 2009-2010 NHANES were used to identify top-ranking sources of dietary sodium among the population aged 2 y and older based on contributions from food categories aligning with the FDA draft guidance for voluntary sodium reduction. Predicted nutrient intakes were estimated in models assuming total and feasible and practical (F&P) replacement of added NaCl with KCl in foods and ingredients within the top food sources of sodium. An expert elicitation was conducted to collect information on the F&P KCl replacement of added NaCl. RESULTS: Using 2015-2016 consumption data, the total replacement of added NaCl with KCl in the 18 top-ranking sources of dietary sodium results in a predicted sodium intake of 2004 mg/d from the replacement of 1406 mg/d sodium with 1870 mg/d potassium as KCl. Modeled F&P replacement predicted sodium intakes of 3117 mg/d (range of 2953 to 3255 mg/d) from the replacement of 294 mg/d sodium (155 to 457 mg/d) with 390 mg/d potassium (206 to 608 mg/d). Similar results are seen with 2009-2010 data. CONCLUSIONS: The F&P replacement of NaCl with KCl in top-ranking sources of dietary sodium modeled in this study can result in decreased sodium to a level consistent with the short-term intake goal targeted by the FDA of 3000 mg/d, with the mean potassium intake remaining in the range recommended for the apparently healthy population.

Tiered intake assessment for low- and no-calorie sweeteners in beverages.

A tiered intake assessment approach is presented and applied to derive the maximum potential global low- and no-calorie sweeteners (LNCS) intake estimates. The US and Uk markets served as representative for the world and the EU region, respectively, to determine the maximum potential exposure for acesulfame potassium (AceK), aspartame, saccharin, steviol glycosides, and sucralose in various subpopulations, including brand-loyal consumers. Conservative intake estimates for LNCS used in non-alcoholic beverages were calculated for the general population 2 + y, toddlers (12-35 months (US) or 18-35 months (UK)), young children 3-9 y, adolescents 10-17 y, adults 18-64 y, elderly 65-74 y, and very elderly 75 + y based on assumed uses in high beverage consumption markets, leveraging either the 2-day food consumption data from the 2013-2016 US National Health and Nutrition Examination Survey or the 4-day food consumption data from the 2008-2017 UK National Diet and Nutrition Survey Rolling Programme. Strong concordance between the refined budget method and the brand-loyal deterministic approach was shown, the latter assumes the maximum industry-reported global LNCS use level is present in 100% of non-alcoholic beverages. This study shows that safety of LNCS in beverages at proposed use levels can be supported for any geography, with all intake estimates falling below the acceptable daily intake in refined assessments. Importantly, this study shows the refined budget method to be a valid first-tier screening assessment in prioritising those LNCS that may benefit from more refined intake assessments when warranted.

Tiered intake assessment for food colours.

A tiered intake assessment approach, ranging from the conservative default and refined budget method to refined dietary exposure assessments using national food consumption surveys is presented and applied to derive maximum potential global colour intake estimates. The US and UK markets served as representative for the world and the EU, respectively, to determine the maximum potential exposure ceilings for eleven colours in various sub-populations, including brand-loyal consumers. Industry-reported global use levels were assigned as the maximum level. Conservative intake assessments for food colours used in non-alcoholic beverages were estimated for the general population 2 + y, toddlers, children 3-9 y, adolescents 10-17 y, adults 18-64 y, elderly 65-74 y, very elderly 75 + y based on assumed uses in high intake markets. Refined dietary exposures were estimated using either the 2-day food consumption data from the 2013-2016 US National Health and Nutrition Examination Survey or the 4-day food consumption data from the 2008-2016 U.K. National Diet and Nutrition Survey Rolling Programme. In the most refined market-share adjusted assessment, brand-specific market volume data were used to place appropriate weight on corresponding beverage type uses. Strong concordance between the refined budget method and the brand-loyal deterministic approach was shown, in which the latter assumes that the maximum use level of the colour is present in 100% of non-alcoholic beverages. This study shows that safety of colours - both synthetic and natural - in beverages at proposed use levels can be supported for any geography, with all intake estimates falling below the acceptable daily intake in refined assessments. Importantly, this study demonstrates that the refined budget method is a valid first-tier screening assessment to prioritise food colours that may benefit from more refined intake assessments when warranted.

Comparisons of Nutrient Intakes and Diet Quality among Water-Based Beverage Consumers.

Americans are encouraged to reduce intake of sugar-sweetened beverages (SSB). Zero and low-calorie water-based beverages can provide alternative options to SSB, though limited data are available to understand measures of diet quality across different beverage consumer groups. The purpose of this cross-sectional study was to quantify intake of added sugars, total sugars, carbohydrates, and diet quality among consumers of zero-calorie unsweetened beverages (ZCUB) compared to SSB; and, separately, among consumers of low- and no-calorie sweetened beverages (LNCSB) when compared to SSB. Dietary data from the 2009⁻2016 National Health and Nutrition Examination Survey (NHANES) were analyzed among three life stages by SSB, ZCUB, and LNCSB consumer groups and adjusted for participant characteristics and energy intake. Across all life stages, ZCUB and LNCSB consumers had lower mean intakes of total sugars, added sugars, and carbohydrates when compared to SSB consumers. Diet quality as measured by the Healthy Eating Index 2015 (HEI-2015) was also higher among ZCUB and LNCSB consumers compared to SSB consumers in analyses adjusted for participant characteristics. These results indicate that reduction of SSB from dietary patterns and replacement with ZCUB or LNCSB could help Americans improve overall diet quality.

Reduction in Dietary Acrylamide Exposure-Impact of Potatoes with Low Acrylamide Potential.

Acrylamide forms primarily from a reaction between reducing sugars (e.g., glucose and fructose) and an amino acid (asparagine, Asn) formed naturally in foods, including potatoes. This reaction occurs when carbohydrate-rich foods are heated at temperatures above 120 °C. Multiple potato varieties were transformed with potato genomic DNA that results in down-regulation of the expression of the asparagine synthetase-1 gene (Asn1), significantly reducing synthesis of free Asn, and consequently lowering the potential to form acrylamide during cooking. These potatoes with low acrylamide potential (LAP) were tested in agronomic trials, and processed into French fries and potato chips. Decreased levels of acrylamide were measured in these cooked food products when derived from LAP potatoes compared with those derived from conventional potatoes. These reductions can be directly attributed to reduction in Asn levels in the LAP potatoes. The corresponding average reduction in exposure to acrylamide from French fry and potato chip consumption is estimated to be 65%, which would amount to approximately a 25% reduction in overall dietary exposure. Considering that children consume nearly three times more acrylamide than adults on a per kg body weight basis, they would experience the most impact from the reduced acrylamide associated with LAP potatoes. The potential public health impacts, in context of dietary acrylamide exposure reduction, are discussed in this study.

Partitioning of Dietary Metal Intake--A Metal Dietary Exposure Screening Tool.

Detection of heavy metals at trace or higher levels in foods and food ingredients is not unexpected given the widespread unavoidable presence of several metals in nature, coupled with advancement in analytical methods and lowering limits of detection. To assist risk managers with a rapid risk assessment when facing these situations, a metal dietary exposure screening tool (MDEST) was developed. The tool uses food intake rates based on the National Health and Nutrition Examination Survey 2005-2010 consumption data for the U.S. population two+ years and up and for infants age six months to

Egg consumption and cardiovascular disease among diabetic individuals: a systematic review of the literature.

BACKGROUND: This study reviewed epidemiological and experimental evidence on the relationship between egg consumption and cardiovascular disease (CVD) risks among type II diabetes mellitus (T2DM) individuals, and T2DM risk in nondiabetic subjects. RESULTS: Four of the six studies that examined CVD and mortality and egg consumption among diabetics found a statistically significant association. Of the eight studies evaluating incident T2DM and egg consumption, four prospective studies found a statistically significant association. Lack of adjustment for dietary confounders was a common study limitation. A small number of experimental studies examined the relationship between egg intake and CVD risk biomarkers among diabetics or individuals with T2DM risk factors. Studies among healthy subjects found suggestive evidence that dietary interventions that include eggs may reduce the risk of T2DM and metabolic syndrome. CONCLUSION: Differences in study design, T2DM status, exposure measurement, subject age, control for confounders and follow-up time present significant challenges for conducting a meta-analysis. Conflicting results, coupled with small sample sizes, prevent broad interpretation. Given the study limitations, these findings need to be further investigated.

Estimated long-term fish and shellfish intake--national health and nutrition examination survey.

Usual intake estimates describe long-term average intake of food and nutrients and food contaminants. The frequencies of fish and shellfish intake over a 30-day period from National Health and Examination Survey (NHANES 1999-2006) were combined with 24-h dietary recall data from NHANES 2003-2004 using a Monte Carlo procedure to estimate the usual intake of fish and shellfish in this study. Usual intakes were estimated for the US population including children 1 to <11 years, males/females 11 to <16 years, 16 to <21 years, and adults 21+ years. Estimated mean fish intake (consumers only) was highest among children 1 to <2 years and 2 to <3 years, at 0.37 g/kg-day for both age groups, and lowest for females 11 to <16 years, at 0.13 g/kg-day. In all age groups, daily intake estimates were highest for breaded fish, salmon, and mackerel. Among children and teenage consumers, tuna, salmon, and breaded fish were the most frequently consumed fish; shrimp, scallops, and crabs were the most frequently consumed shellfish. The intake estimates from this study better reflect long-term average intake rates and are preferred to assess long-term intake of nutrients and possible exposure to environmental contaminants from fish and shellfish sources than 2-day average estimates.

Egg consumption and CHD and stroke mortality: a prospective study of US adults.

OBJECTIVE: To evaluate the relationship between egg consumption and CHD and stroke mortality using the Third National Health and Nutrition Examination Survey 1988-1994 (NHANES III) and follow-up survey. DESIGN: A cross-sectional survey using a stratified, multi-stage probability sample was analysed, adjusting for survey design. Egg consumption was obtained from the FFQ and separated into categories of egg intake. Hazard ratios (HR) were calculated for CHD and stroke mortality using multivariate Cox regression models. SETTING: A health and nutrition survey conducted in the USA from 1988 to 1994 with follow-up through 31 December 2000. SUBJECTS: The study population included men and women who were free of CVD and had completed a FFQ at baseline. RESULTS: Multivariate models adjusting for health, lifestyle and dietary factors indicated that 'high' egg consumption (≥ 7 times/week v. <1 time/week) was not associated with significantly increased CHD mortality (HR = 1·13, 95 % CI 0·61, 2·11 (men); HR = 0·92, 95 % CI 0·27, 3·11 (women)). There was a statistically significant inverse association between 'high' egg consumption and stroke mortality among men (HR = 0·27, 95 % CI 0·10, 0·73), but the estimate was imprecise because of sparse data. We did not observe a statistically significant positive association between 'high' egg consumption and CHD or stroke mortality in analyses restricted to individuals with diabetes, but these analyses may be limited due to the small number of diabetics. CONCLUSIONS: We did not find a significant positive association between egg consumption and increased risk of mortality from CHD or stroke in the US population. These results corroborate the findings of previous studies.

Partially hydrolyzed 100% whey protein infant formula and atopic dermatitis risk reduction: a systematic review of the literature.

The incidence of atopic dermatitis (AD) is increasing worldwide. Clinical studies have observed reduced risks of AD among infants fed with 100% whey partially hydrolyzed infant formula (PHF-W) compared with intact protein cow's milk formula. To evaluate this potential relationship more comprehensively, a systematic review of the literature was conducted. Studies (n = 18, representing 12 distinct study populations) that specified the protein source of the formula, evaluated healthy-term infants, compared the use of PHF-W with intact protein cow's milk formula, and reported results for AD were included. A critical assessment of the methodological quality of studies was conducted. In all studies, a reduced incidence of AD and/or atopic manifestations that included AD was observed. The cumulative incidence of AD was significantly lower among infants over at least 3 years of follow-up in the PHF-W group compared with the intact protein cow's milk group. Exclusive breastfeeding should be encouraged as the primary means to prevent atopic risk. However, when infants are not exclusively breastfed, PHF-W may be considered an effective measure to potentially reduce the risk of developing AD.

Single food focus dietary guidance: lessons learned from an economic analysis of egg consumption.

BACKGROUND: There is a large body of literature evaluating the impact of various nutrients of eggs and their dietary cholesterol content on health conditions. There is also literature on the costs of each condition associated with egg consumption. The goal of the present study is to synthesize what is known about the risks and benefits of eggs and the associated costs from a societal perspective. METHODS: A risk apportionment model estimated the increased risk for coronary heart disease (CHD) attributable to egg cholesterol content, the decreased risk for other conditions (age-related macular degeneration (AMD), cataract, neural tube defects, and sarcopenia) associated with egg consumption, and a literature search identified the cost of illness of each condition. The base 795 case scenario calculated the costs or savings of each condition attributable to egg cholesterol or nutrient content. RESULTS: Given the costs associated with CHD and the benefits associated with the other conditions, the most likely scenario associated with eating an egg a day is savings of $2.82 billion annually with uncertainty ranging from a net cost of $756 million to net savings up to $8.50 billion. CONCLUSION: This study evaluating the economic impact of egg consumption suggests that public health campaigns promoting limiting egg consumption as a means to reduce CHD risk would not be cost-effective from a societal perspective when other benefits are considered. Public health intervention that focuses on a single dietary constituent, and foods that are high in that constituent, may lead to unintended consequences of removing other beneficial constituents and the net effect may not be in its totality a desirable public health outcome. As newer data become available, the model should be updated.

Perspective: risk apportionment and disease intervention strategies.

The ultimate public health objective is the ability to predict and prevent disease, and not necessarily to identify an exhaustive list of potential disease risk factors. For any important public health outcome with multiple and potentially interrelated risk factors, an improved understanding of the contribution of individual and combinations of modifiable risk factors to the disease burden is essential for formulating an appropriate public health strategy. Partitioning techniques that divide the combined impact of multiple risk factors into exposure-specific components while taking into account the potential interrelations among those components, have been described in the epidemiological literature. In this article, we review and compare the available methods and options for such apportionment and apply them in a more general public health context as a method of selecting and prioritizing coronary heart disease (CHD) prevention strategies.

Toxicological resources for cumulative risk: an example with hazardous air pollutants.

Cumulative risk assessment, concerned with the multiple health effects of chemical mixtures, challenges the utility of existing single-chemical regulatory references. We compare example cumulative risk assessments for 40 HAPs; one based on single-effect toxicological data from EPA, and another based on a multiple-effect toxicological database we developed. For the 40-chemical HAP subset, the multiple effect database contains information on approximately seven effects per chemical and contains a total of 290 toxicological values. Seven health effects are represented in the IRIS data. Seventeen health effects are represented in the multiple-effect data. Respiratory and neurological effects ranked first and second in both cumulative analyses, regardless of the source data. In addition to respiratory and neurological effects, gastro-intestinal/hepatic, renal/kidney, and immunologic effects were identified as effects of concern on the basis of the multiple effect data. Immunologic effects are not found in the 40-chemical IRIS dataset. Cumulative risk assessment has the potential to expand our understanding of the public health impacts of environmental exposures. Advancements in toxicological resources will improve cumulative risk assessment. Cumulative risk assessment will reduce risks to the extent that it can be integrated into prevention strategies to track and protect the public's health.

Combining food frequency and survey data to quantify long-term dietary exposure: a methyl mercury case study.

Twenty-four-hour recall data from the Continuing Survey of Food Intake by Individuals (CSFII) are frequently used to estimate dietary exposure for risk assessment. Food frequency questionnaires are traditional instruments of epidemiological research; however, their application in dietary exposure and risk assessment has been limited. This article presents a probabilistic method of bridging the National Health and Nutrition Examination Survey (NHANES) food frequency and the CSFII data to estimate longitudinal (usual) intake, using a case study of seafood mercury exposures for two population subgroups (females 16 to 49 years and children 1 to 5 years). Two hundred forty-nine CSFII food codes were mapped into 28 NHANES fish/shellfish categories. FDA and state/local seafood mercury data were used. A uniform distribution with minimum and maximum blood-diet ratios of 0.66 to 1.07 was assumed. A probabilistic assessment was conducted to estimate distributions of individual 30-day average daily fish/shellfish intakes, methyl mercury exposure, and blood levels. The upper percentile estimates of fish and shellfish intakes based on the 30-day daily averages were lower than those based on two- and three-day daily averages. These results support previous findings that distributions of "usual" intakes based on a small number of consumption days provide overestimates in the upper percentiles. About 10% of the females (16 to 49 years) and children (1 to 5 years) may be exposed to mercury levels above the EPA's RfD. The predicted 75th and 90th percentile blood mercury levels for the females in the 16-to-49-year group were similar to those reported by NHANES. The predicted 90th percentile blood mercury levels for children in the 1-to-5-year subgroup was similar to NHANES and the 75th percentile estimates were slightly above the NHANES.

Examining urban brownfields through the public health "macroscope".

Efforts to cope with the legacy of our industrial cities--blight, poverty, environmental degradation, ailing communities--have galvanized action across the public and private sectors to move vacant industrial land, also referred to as brownfields, to productive use; to curb sprawling development outside urban areas; and to reinvigorate urban communities. Such efforts, however, may be proceeding without thorough investigations into the environmental health and safety risks associated with industrial brownfields properties and the needs of affected neighborhoods. We describe an approach to characterize vacant and underused industrial and commercial properties in Southeast Baltimore and the health and well being of communities living near these properties. The screening algorithm developed to score and rank properties in Southeast Baltimore (n= 182) showed that these sites are not benign. The historical data revealed a range of hazardous operations, including metal smelting, oil refining, warehousing, and transportation, as well as paints, plastics, and metals manufacturing. The data also identified hazardous substances linked to these properties, including heavy metals, solvents, polycyclic aromatic hydrocarbons, plasticizers, and insecticides, all of which are suspected or recognized toxicants and many of which are persistent in the environment. The health analysis revealed disparities across Southeast Baltimore communities, including excess deaths from respiratory illness (lung cancer, chronic obstructive pulmonary disease, influenza, and pneumonia), total cancers, and a "leading cause of death" index and a spatial and statistical relationship between environmentally degraded brownfields areas and at-risk communities. Brownfields redevelopment is a key component of our national efforts to address environmental justice and health disparities across urban communities and is critical to urban revitalization. Incorporating public health into brownfields-related cleanup and land-use decisions will increase the odds for successful neighborhood redevelopment and long-term public health benefits.