Acute and two-week effects of neotame, stevia rebaudioside M and sucrose-sweetened biscuits on postprandial appetite and endocrine response in adults with overweight/obesity-a randomised crossover trial from the SWEET consortium.

BACKGROUND: Sweeteners and sweetness enhancers (S&SE) are used to replace energy yielding sugars and maintain sweet taste in a wide range of products, but controversy exists about their effects on appetite and endocrine responses in reduced or no added sugar solid foods. The aim of the current study was to evaluate the acute (1 day) and repeated (two-week daily) ingestive effects of 2 S&SE vs. sucrose formulations of biscuit with fruit filling on appetite and endocrine responses in adults with overweight and obesity. METHODS: In a randomised crossover trial, 53 healthy adults (33 female, 20 male) with overweight/obesity in England and France consumed biscuits with fruit filling containing 1) sucrose, or reformulated with either 2) Stevia Rebaudioside M (StRebM) or 3) Neotame daily during three, two-week intervention periods with a two-week washout. The primary outcome was composite appetite score defined as [desire to eat + hunger + (100 - fullness) + prospective consumption]/4. FINDINGS: Each formulation elicited a similar reduction in appetite sensations (3-h postprandial net iAUC). Postprandial insulin (2-h iAUC) was lower after Neotame (95% CI (0.093, 0.166); p < 0.001; d = -0.71) and StRebM (95% CI (0.133, 0.205); p < 0.001; d = -1.01) compared to sucrose, and glucose was lower after StRebM (95% CI (0.023, 0.171); p < 0.05; d = -0.39) but not after Neotame (95% CI (-0.007, 0.145); p = 0.074; d = -0.25) compared to sucrose. There were no differences between S&SE or sucrose formulations on ghrelin, glucagon-like peptide 1 or pancreatic polypeptide iAUCs. No clinically meaningful differences between acute vs. two-weeks of daily consumption were found. INTERPRETATION: In conclusion, biscuits reformulated to replace sugar using StRebM or Neotame showed no differences in appetite or endocrine responses, acutely or after a two-week exposure, but can reduce postprandial insulin and glucose response in adults with overweight or obesity. FUNDING: The present study was funded by the Horizon 2020 program: Sweeteners and sweetness enhancers: Impact on health, obesity, safety and sustainability (acronym: SWEET, grant no: 774293).

Fat-free mass and resting metabolic rate are determinants of energy intake: implications for a theory of appetite control.

Any explanation of appetite control should contain a description of physiological processes that could contribute a drive to eat alongside those that inhibit eating. However, such an undertaking was largely neglected until 15 years ago when a series of independent research programmes investigated the physiological roles of body composition and appetite. These outcomes demonstrated that fat-free mass (FFM), but not fat mass, was positively associated with objectively measured meal size and energy intake (EI). These findings have been accompanied by demonstrations that resting metabolic rate (RMR) is also positively associated with EI, with the influence of FFM largely mediated by RMR. These findings re-introduce the role of drive into models of appetite control and indicate how this can be integrated with processes of inhibition. The determinants of EI fit into an evolutionary perspective in which the energy demands of high metabolic rate organs and skeletal tissue constitute a need state underlying a tonic drive to eat. This approach should lead to the development of integrated models of appetite that include components of body composition (FFM) and energy expenditure (RMR) as tonic biological signals of appetite alongside other traditional tonic (adipose tissue derived) and episodic signals (gastrointestinal tract derived). This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part I)'.

Do eating behavior traits predict energy intake and body mass index? A systematic review and meta-analysis.

At present, it is unclear whether eating behavior traits (EBT) predict objectively measured short-term energy intake (EI) and longer-term energy balance as estimated by body mass index (BMI). This systematic review examined the impact of EBT on BMI and laboratory-based measures of EI in adults ( ≥ 18 years) in any BMI category, excluding self-report measures of EI. Articles were searched up until 28th October 2021 using MEDLINE, PsycINFO, EMBASE and Web of Science. Sixteen EBT were identified and the association between 10 EBT, EI and BMI were assessed using a random-effects meta-analysis. Other EBT outcomes were synthesized qualitatively. Risk of bias was assessed with the mixed methods appraisal tool. A total of 83 studies were included (mean BMI = 25.20 kg/m2 , mean age = 27 years and mean sample size = 70). Study quality was rated moderately high overall, with some concerns in sampling strategy and statistical analyses. Susceptibility to hunger (n = 6) and binge eating (n = 7) were the strongest predictors of EI. Disinhibition (n = 8) was the strongest predictor of BMI. Overall, EBT may be useful as phenotypic markers of susceptibility to overconsume or develop obesity (PROSPERO: CRD42021288694).

Acute and repeated impact of sweeteners and sweetness enhancers in solid and semi-solid foods on appetite: protocol for a multicentre, cross-over, RCT in people with overweight/obesity - the SWEET Project.

INTRODUCTION: Intake of free sugars in European countries is high and attempts to reduce sugar intake have been mostly ineffective. Non-nutritive sweeteners and sweetness enhancers (S&SEs) can maintain sweet taste in the absence of energy, but little is known about the impact of acute and repeated consumption of S&SE in foods on appetite. This study aims to evaluate the effect of acute and repeated consumption of two individual S&SEs and two S&SE blends in semisolid and solid foods on appetite and related behavioural, metabolic and health outcomes. METHODS AND ANALYSIS: A work package of the SWEET Project; this study consists of five double-blind randomised cross-over trials which will be carried out at five sites across four European countries, aiming to have n=213. Five food matrices will be tested across three formulations (sucrose-sweetened control vs two reformulated products with S&SE blends and no added sugar). Participants (body mass index 25-35 kg/m2; aged 18-60 years) will consume each formulation for 14 days. The primary endpoint is composite appetite score (hunger, inverse of fullness, desire to eat and prospective food consumption) over a 3-hour postprandial incremental area under the curve during clinical investigation days on days 1 and 14. ETHICS AND DISSEMINATION: The trial has been approved by national ethical committees and will be conducted in accordance with the Declaration of Helsinki. Results will be published in international peer-reviewed open-access scientific journals. Research data from the trial will be deposited in an open-access online research data archive. TRIAL REGISTRATION NUMBER: NCT04633681.

Systematic evidence map (SEM) template: Report format and methods used for the US EPA Integrated Risk Information System (IRIS) program, Provisional Peer Reviewed Toxicity Value (PPRTV) program, and other "fit for purpose" literature-based human health analyses.

BACKGROUND: Systematic evidence maps (SEMs) are gaining visibility in environmental health for their utility to serve as problem formulation tools and assist in decision-making, especially for priority setting. SEMs are now routinely prepared as part of the assessment development process for the US Environmental Protection Agency (EPA) Integrated Risk Information System (IRIS) and Provisional Peer Reviewed Toxicity Value (PPRTV) assessments. SEMs can also be prepared to explore the available literature for an individual chemical or groups of chemicals of emerging interest. OBJECTIVES: This document describes the typical methods used to produce SEMs for the IRIS and PPRTV Programs, as well as "fit for purpose" applications using a variety of examples drawn from existing analyses. It is intended to serve as an example base template that can be adapted as needed for the specific SEM. The presented methods include workflows intended to facilitate rapid production. The Populations, Exposures, Comparators and Outcomes (PECO) criteria are typically kept broad to identify mammalian animal bioassay and epidemiological studies that could be informative for human hazard identification. In addition, a variety of supplemental content is tracked, e.g., studies presenting information on in vitro model systems, non-mammalian model systems, exposure-level-only studies in humans, pharmacokinetic models, and absorption, distribution, metabolism, and excretion (ADME). The availability of New Approach Methods (NAMs) evidence is also tracked (e.g., high throughput, transcriptomic, in silico, etc.). Genotoxicity studies may be considered as PECO relevant or supplemental material, depending on the topic and context of the review. Standard systematic review practices (e.g., two independent reviewers per record) and specialized software applications are used to search and screen the literature and may include the use of machine learning software. Mammalian bioassay and epidemiological studies that meet the PECO criteria after full-text review are briefly summarized using structured web-based extraction forms with respect to study design and health system(s) assessed. Extracted data is available in interactive visual formats and can be downloaded in open access formats. Methods for conducting study evaluation are also presented which is conducted on a case-by-case basis, depending on the usage of the SEM.

Use of systematic evidence maps within the US environmental protection agency (EPA) integrated risk information system (IRIS) program: Advancements to date and looking ahead.

Systematic evidence maps (SEMs) are increasingly used to inform decision-making and risk management priority-setting and to serve as problem formulation tools to refine the focus of questions that get addressed in full systematic reviews. Within the U.S. Environmental Protection Agency (EPA) Office of Research and Development (ORD) Integrated Risk Information System (IRIS), SEMs have been used to inform data gaps, determine the need for updated assessments, inform assessment priorities, and inform development of study evaluation considerations, among other uses. Increased utilization of SEMs across the environmental health field has the potential to increase transparency and efficiency for data gathering, problem formulation, read-across, and evidence surveillance. Use of the SEM templates published in the companion text (Thayer et al.) can promote harmonization in the environmental health community and create more opportunities for sharing extracted content.

Increases in physical activity are associated with a faster rate of weight loss during dietary energy restriction in women with overweight and obesity.

This secondary analysis examined the influence of changes in physical activity (PA), sedentary time and energy expenditure (EE) during dietary energy restriction on the rate of weight loss (WL) and 1-year follow-up weight change in women with overweight/obesity.Measurements of body weight and composition (air-displacement plethysmography), resting metabolic rate (indirect calorimetry), total daily (TDEE) and activity EE (AEE), minutes of PA and sedentary time (PA monitor) were taken at baseline, after 2 weeks, after ≥5% WL or 12 weeks of continuous (25% daily energy deficit) or intermittent (75% daily energy deficit alternated with ad libitum day) energy restriction, and at 1-year post-WL. The rate of WL was calculated as total %WL/number of dieting weeks. Data from both groups were combined for analyses.Thirty-seven participants (age=35±10y; BMI=29.1±2.3kg/m2) completed the intervention (WL=-5.9±1.6%) and 18 returned at 1-year post-WL (weight change=+4.5±5.2%). Changes in sedentary time at 2 weeks were associated with the rate of WL during energy restriction (r=-0.38; p=0.03). Changes in total (r=0.54; p<0.01), light (r=0.43; p=0.01) and moderate-to-vigorous PA (r=0.55; p<0.01), sedentary time (r=-0.52; p<0.01), steps per day (r=0.39; p=0.02), TDEE (r=0.46; p<0.01) and AEE (r=0.51; p<0.01) during energy restriction were associated with the rate of WL. Changes in total (r=-0.50; p=0.04) and moderate-to-vigorous PA (r=-0.61; p=0.01) between post-WL and follow-up were associated with 1-year weight change (r=-0.51; p=0.04).These findings highlight that PA and sedentary time could act as modifiable behavioural targets to promote better weight outcomes during dietary energy restriction and/or weight maintenance.

Free-Living Energy Balance Behaviors Are Associated With Greater Weight Loss During a Weight Loss Program.

Introduction: Free-living movement (physical activity [PA] and sedentary behavior [SB]) and eating behaviors (energy intake [EI] and food choice) affect energy balance and therefore have the potential to influence weight loss (WL). This study explored whether free-living movement and/or eating behaviors measured early (week 3) in a 14-week WL programme or their change during the intervention are associated with WL in women. Methods: In the study, 80 women (M ± SD age: 42.0 ± 12.4 years) with overweight or obesity [body mass index (BMI): 34.08 ± 3.62 kg/m2] completed a 14 week WL program focused primarily on diet (commercial or self-led). Body mass (BM) was measured at baseline, and again during week 2 and 14 along with body composition. Free-living movement (SenseWear Armband) and eating behavior (weighed food diaries) were measured for 1 week during week 3 and 12. Hierarchical multiple regression analyses examined whether early and early-late change in free-living movement and eating behavior were associated with WL. The differences in behavior between clinically significant weight losers (CWL; ≥5% WL) and non-clinically significant weight losers (NWL; ≤ 3% WL) were compared. Results: The energy density of food consumed [ß = 0.45, p < 0.001] and vigorous PA [ß = -0.30, p < 0.001] early in the intervention (regression model 1) and early-late change in light PA [ß = -0.81 p < 0.001], moderate PA [ß = -1.17 p < 0.001], vigorous PA [ß = -0.49, p < 0.001], total energy expenditure (EE) [ß = 1.84, p < 0.001], and energy density of food consumed [ß = 0.27, p = 0.01] (regression model 2) significantly predicted percentage change in BM. Early in the intervention, CWL consumed less energy dense foods than NWL [p = 0.03]. CWL showed a small but significant increase in vigorous PA, whereas NWL showed a slight decrease in PA [p = 0.04]. Conclusion: Both early and early-late change in free-living movement and eating behaviors during a 14 week WL program are predictors of WL. These findings demonstrate that specific behaviors that contribute to greater EE (e.g., vigorous PA) and lower EI (e.g., less energy-dense foods) are related to greater WL outcomes. Interventions targeting these behaviors can be expected to increase the effectiveness of WL programs.

Evaluation of Existing QSAR Models and Structural Alerts and Development of New Ensemble Models for Genotoxicity Using a Newly Compiled Experimental Dataset.

Regulatory agencies world-wide face the challenge of performing risk-based prioritization of thousands of substances in commerce. In this study, a major effort was undertaken to compile a large genotoxicity dataset (54,805 records for 9299 substances) from several public sources (e.g., TOXNET, COSMOS, eChemPortal). The names and outcomes of the different assays were harmonized, and assays were annotated by type: gene mutation in Salmonella bacteria (Ames assay) and chromosome mutation (clastogenicity) in vitro or in vivo (chromosome aberration, micronucleus, and mouse lymphoma Tk +/- assays). This dataset was then evaluated to assess genotoxic potential using a categorization scheme, whereby a substance was considered genotoxic if it was positive in at least one Ames or clastogen study. The categorization dataset comprised 8442 chemicals, of which 2728 chemicals were genotoxic, 5585 were not and 129 were inconclusive. QSAR models (TEST and VEGA) and the OECD Toolbox structural alerts/profilers (e.g., OASIS DNA alerts for Ames and chromosomal aberrations) were used to make in silico predictions of genotoxicity potential. The performance of the individual QSAR tools and structural alerts resulted in balanced accuracies of 57-73%. A Naïve Bayes consensus model was developed using combinations of QSAR models and structural alert predictions. The 'best' consensus model selected had a balanced accuracy of 81.2%, a sensitivity of 87.24% and a specificity of 75.20%. This in silico scheme offers promise as a first step in ranking thousands of substances as part of a prioritization approach for genotoxicity.

Effects of oral lubrication on satiety, satiation and salivary biomarkers in model foods: A pilot study.

With a dramatic increase in overweight and population with obesity over the last decades, there is an imminent need to tackle this issue using novel strategies. Addressing obesity issues by generating satiety in food to reduce energy intake has been one of those prominent strategies and often textural interventions have been used to generate satiety, specifically in short-term trials. This study aimed to investigate the role of preloads varying in their oral lubricating properties on appetite sensations, food intake, salivary friction and concentration of salivary biomarkers (proteins, α-amylase and mucins) in collected human saliva (n = 17 healthy participants). The preloads were model foods (flavoured hydrogels) either high or low in their lubricating properties, assessed both by instrumental and sensorial measurements. The results showed that hunger and desire to eat decreased immediately after preload and remained decreased for 10 and 20 min, respectively, after preload in the high lubricating condition compared to control (all p < 0.05). Fullness increased immediately after preload and remained increased for 10 and 20 min, respectively, after preload in high lubricating condition compared to control (p < 0.05). However, after controlling the values for baseline, such significant effect of the intervention did not exist anymore. Only the effect of time is observed. Consuming high lubricating hydrogels showed no effect on food intake and salivary biomarkers in this pilot study. Salivary lubrication correlated with feeling of fullness. Considering the issue of large time-interval (30 min) between preload and next meal in this study, it is worthwhile investigating the immediate effects of oral lubrication on appetite control, food intake and salivary biomarkers.

Applying evidence-based methods to the development and use of adverse outcome pathways

The workshop "Application of evidence-based methods to construct mechanistic frameworks for the development and use of non-animal toxicity tests" was organized by the Evidence-based Toxicology Collaboration and hosted by the Grading of Recommendations Assessment, Development and Evaluation Working Group on June 12, 2019. The purpose of the workshop was to bring together international regulatory bodies, risk assessors, academic scientists, and industry to explore how systematic review methods and the adverse outcome pathway framework could be combined to develop and use mechanistic test methods for predicting the toxicity of chemical substances in an evidence-based manner. The meeting covered the history of biological frameworks, the way adverse outcome pathways are currently developed, the basic principles of systematic methodology, including systematic reviews and evidence maps, and assessment of cer­tainty in models, and adverse outcome pathways in particular. Specific topics were discussed via case studies in small break-out groups. The group concluded that adverse outcome pathways provide an important framework to support mechanism-based assessment in environmental health. The process of their development has a few challenges that could be addressed with systematic methods and automation tools. Addressing these challenges will increase the transparency of the evidence behind adverse outcome pathways and the consistency with which they are defined; this in turn will increase their value for supporting public health decisions. It was suggested to explore the details of applying systematic methods to adverse outcome pathway development in a series of case studies and workshops.

Food Liking but Not Wanting Decreases after Controlled Intermittent or Continuous Energy Restriction to ≥5% Weight Loss in Women with Overweight/Obesity.

Food reward (i.e., liking and wanting) has been shown to decrease after different types of weight management interventions. However, it is unknown whether specific dietary modalities (continuous (CER) vs. intermittent (IER) energy restriction) have differing effects on liking and implicit wanting after weight loss (WL) and whether these changes are sustained after 1-year of no-contact. Women with overweight or obesity (age 18-55 years) were randomly allocated to controlled-feeding CER (25% daily energy restriction) or IER (alternating ad libitum and 75% energy restriction days). Study visits were conducted at baseline, post-WL (to ≥5% WL within 12 weeks) and 1-year post-WL. The main outcomes were liking and implicit wanting for 4 categories of common food varying in fat and taste assessed by the Leeds Food Preference Questionnaire. Linear mixed models were conducted on the 30 participants achieving ≥5% WL and 15 returners. After an initial WL of -5.1 ± 0.2 kg, after 1-year 2.6 ± 0.5 kg were regained. Liking but not wanting decreased after WL. Food reward after 1-year did not differ from baseline, but the high loss to follow-up prevents generalization. IER and CER did not differ in their effects on food reward during WL or at 1-year follow-up.

A rational review on the effects of sweeteners and sweetness enhancers on appetite, food reward and metabolic/adiposity outcomes in adults.

Numerous strategies have been investigated to overcome the excessive weight gain that accompanies a chronic positive energy balance. Most approaches focus on a reduction of energy intake and the improvement of lifestyle habits. The use of high intensity artificial sweeteners, also known as non-caloric sweeteners (NCS), as sugar substitutes in foods and beverages, is rapidly developing. NCS are commonly defined as molecules with a sweetness profile of 30 times higher or more that of sucrose, scarcely contributing to the individual's net energy intake as they are hardly metabolized. The purpose of this review is first, to assess the impact of NCS on eating behaviour, including subjective appetite, food intake, food reward and sensory stimulation; and secondly, to assess the metabolic impact of NCS on body weight regulation, glucose homeostasis and gut health. The evidence reviewed suggests that while some sweeteners have the potential to increase subjective appetite, these effects do not translate in changes in food intake. This is supported by a large body of empirical evidence advocating that the use of NCS facilitates weight management when used alongside other weight management strategies. On the other hand, although NCS are very unlikely to impair insulin metabolism and glycaemic control, some studies suggest that NCS could have putatively undesirable effects, through various indirect mechanisms, on body weight, glycemia, adipogenesis and the gut microbiota; however there is insufficient evidence to determine the degree of such effects. Overall, the available data suggests that NCS can be used to facilitate a reduction in dietary energy content without significant negative effects on food intake behaviour or body metabolism, which would support their potential role in the prevention of obesity as a complementary strategy to other weight management approaches. More research is needed to determine the impact of NCS on metabolic health, in particular gut microbiota.

Effects of oral semaglutide on energy intake, food preference, appetite, control of eating and body weight in subjects with type 2 diabetes.

AIM: To evaluate the effect of oral semaglutide on energy intake and appetite in subjects with type 2 diabetes (T2D). MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled, two-period cross-over trial, 15 subjects with T2D received 12 weeks of treatment with once-daily oral semaglutide (4-week dose escalation from 3 to 7 to 14 mg) followed by placebo, or vice versa. Energy intake was measured during an ad libitum lunch, evening meal and snack box after a standard breakfast. Appetite ratings were measured using a visual analogue scale after standard and fat-rich breakfasts. Other assessments included eating and craving control (using the Control of Eating Questionnaire), and changes in body weight and composition. RESULTS: Following a standard breakfast, total daily ad libitum energy intake was significantly lower (38.9%) with oral semaglutide versus placebo in 13 evaluable subjects (estimated treatment difference, -5096.0 kJ; 95% CI -7000.0, -3192.1; P = .0001). After a fat-rich breakfast, there were significant differences in favour of oral semaglutide versus placebo for measures of satiety, hunger and for overall appetite score, with no significant differences following a standard breakfast. Fewer food cravings and better eating control were seen with oral semaglutide versus placebo. Overall, mean body weight decreased by 2.7 kg with oral semaglutide and 0.1 kg with placebo, mostly attributable to body fat mass loss. CONCLUSION: After 12 weeks of treatment, ad libitum energy intake was lower with oral semaglutide versus placebo, resulting in reduced body fat mass, and was associated with increased satiety and fullness after a fat-rich breakfast, and improved eating control. TRIAL REGISTRATION NUMBER: NCT02773381.

An exploratory investigation of the impact of 'fast' and 'feed' days during intermittent energy restriction on free-living energy balance behaviours and subjective states in women with overweight/obesity.

BACKGROUND/OBJECTIVES: This controlled-feeding randomised controlled trial examined free-living appetite and physical activity (PA) on 'fast' and 'feed' days during intermittent energy restriction (IER), compared to continuous energy restriction (CER). SUBJECTS/METHODS: Forty-six women with overweight/obesity (age = 35 ± 10 years, BMI = 29.1 ± 2.3 kg/m2) were randomised to IER (n = 24; alternate fast days at 25% energy requirements and ad libitum feed days) or CER (n = 22; 75% energy requirements daily) to ≥5% weight loss (WL) or up to 12 weeks. Self-reported energy intake (EI; online food record), objectively measured PA (SenseWear Armband) and retrospective daily hunger and food cravings were measured over 7 days at baseline, week 2 and final week. Intent-to-treat analyses were performed using linear mixed models. RESULTS: Final WL (MΔ = 4.7 [95% confidence interval 4.2, 5.2] kg, 5.9%) did not differ between IER and CER (interaction P = 0.307). During IER, feed-day EI did not differ from baseline and was lower in the final week compared to week 2 (MΔ = 295 [81, 509] kcal, P = 0.004). Daily hunger was greater on fast compared to feed days (MΔ = 15 [10, 21] mm, P < 0.001), but food cravings did not differ. Light PA was lower on fast relative to feed days (MΔ = 18 [2, 34] min/day, P = 0.024), with no other differences in PA. Compared to CER, IER increased hunger and led to smaller improvements in craving control (both interactions P ≤ 0.034). CONCLUSIONS: IER fast days were associated with increased free-living hunger and lower light PA compared to feed days, but had no impact on food cravings or self-reported ad libitum daily EI. IER may be less favourable than CER for the free-living day-to-day control of hunger and food cravings.

Integrating publicly available information to screen potential candidates for chemical prioritization under the Toxic Substances Control Act: A proof of concept case study using genotoxicity and carcinogenicity.

The Toxic Substances Control Act (TSCA) became law in the U.S. in 1976 and was amended in 2016. The amended law requires the U.S. EPA to perform risk-based evaluations of existing chemicals. Here, we developed a tiered approach to screen potential candidates based on their genotoxicity and carcinogenicity information to inform the selection of candidate chemicals for prioritization under TSCA. The approach was underpinned by a large database of carcinogenicity and genotoxicity information that had been compiled from various public sources. Carcinogenicity data included weight-of-evidence human carcinogenicity evaluations and animal cancer data. Genotoxicity data included bacterial gene mutation data from the Salmonella (Ames) and Escherichia coli WP2 assays and chromosomal mutation (clastogenicity) data. Additionally, Ames and clastogenicity outcomes were predicted using the alert schemes within the OECD QSAR Toolbox and the Toxicity Estimation Software Tool (TEST). The evaluation workflows for carcinogenicity and genotoxicity were developed along with associated scoring schemes to make an overall outcome determination. For this case study, two sets of chemicals, the TSCA Active Inventory non-confidential portion list available on the EPA CompTox Chemicals Dashboard (33,364 chemicals, 'TSCA Active List') and a representative proof-of-concept (POC) set of 238 chemicals were profiled through the two workflows to make determinations of carcinogenicity and genotoxicity potential. Of the 33,364 substances on the 'TSCA Active List', overall calls could be made for 20,371 substances. Here 46.67%% (9507) of substances were non-genotoxic, 0.5% (103) were scored as inconclusive, 43.93% (8949) were predicted genotoxic and 8.9% (1812) were genotoxic. Overall calls for genotoxicity could be made for 225 of the 238 POC chemicals. Of these, 40.44% (91) were non-genotoxic, 2.67% (6) were inconclusive, 6.22% (14) were predicted genotoxic, and 50.67% (114) genotoxic. The approach shows promise as a means to identify potential candidates for prioritization from a genotoxicity and carcinogenicity perspective.

The compensatory effect of exercise on physical activity and energy intake in young men with overweight: The EFECT randomised controlled trial.

BACKGROUND: The compensatory effect of exercise on total volume of physical activity and food intake has been described as a possible explanation for the limited body weight loss observed during exercise interventions. OBJECTIVE: To investigate the effect of different exercise intensities on total volume of physical activity and energy intake amongst active men with overweight. DESIGN: Young men with overweight from a naval academy (n = 72; mean ± SD, age 21 ± 2 years, BMI 27.9 ± 2.13 kg/m2) were randomised to a control group (CG), moderate-intensity (MEG), or vigorous-intensity exercise group (VEG). MEG and VEG performed exercise sessions three times per week, for 60 min, during a 2-week period. Physical activity was assessed using triaxial accelerometers for 13 days. Energy intake was assessed at four time-points by 24-hour food recall. Intention-to-treat analyses were performed using linear mixed effect models. RESULTS: MEG and VEG presented a greater compensatory effect in the total volume of physical activity over time compared to CG, with a significant difference in the rate of change between VEG and CG (∆ = -250,503 counts vs. ∆ = -61,306 counts, respectively; p = 0.01), and MEG and CG (∆ = -253,336 counts vs. ∆ = -61,306 counts, respectively; p = 0.01). There was no difference between MEG and VEG (p = 0.97). Changes in energy intake were not different between groups (p = 0.18); however, MEG presented greater energy intake compared to CG (ß=491 kcal/day; p = 0.01) and VEG (ß=319 kcal/day; p = 0.07). VEG presented a greater reduction in body weight compared to MEG (-1.3 kg vs. -0.4 kg; p = 0.03) and CG (-1.3 kg vs. -0.6 kg; p = 0.07). CONCLUSIONS: Two weeks of exercise promoted a compensatory effect in total volume of physical activity in active men with overweight, regardless of exercise intensity. The compensatory effect was not observed for energy intake, although there was a trend for higher absolute energy intake in the MEG. Consequently, individuals in the VEG showed greater reduction in body weight over the intervention period.

Body Fatness Influences Associations of Body Composition and Energy Expenditure with Energy Intake in Healthy Women.

OBJECTIVE: This study aimed to investigate the influence of body fatness on the associations of body composition and energy expenditure (EE) with energy intake (EI). METHODS: Data from 93 women (BMI = 25.5 [SD 4.2] kg/m2 ) recruited for two studies (Study 1, n = 48, BMI = 25.0-34.9 kg/m2 ; Study 2, n = 45, BMI = 18.5-24.9 kg/m2 ) were examined. Body composition, resting metabolic rate (RMR), and test meal EI were assessed during a laboratory probe day. Physical activity, total daily EE (TDEE), and self-reported free-living 24-hour EI were collected during 7 days. RESULTS: In the whole sample, fat-free mass (r = 0.45; P < 0.001), RMR (r = 0.41; P < 0.001), and TDEE (r = 0.39; P < 0.001), but not fat mass (r = 0.17; P = 0.11), were positively associated with free-living 24-hour EI. Body fat percentage moderated the associations of RMR (ß = -1.88; P = 0.02) and TDEE (ß = -1.91; P = 0.03) with mean free-living 24-hour EI. Fat mass was negatively associated with test meal EI only in the leaner group (r = -0.43; P = 0.004), and a weak nonlinear association was observed in the whole sample (r2 = 0.092; P = 0.04). CONCLUSIONS: Body fat percentage appears to moderate the associations between EE and daily EI. Furthermore, the negative association between fat mass and test meal EI observed in leaner individuals was absent in those with higher body fatness. Therefore, higher levels of body fatness may weaken the coupling between EE and EI.