Simple, fast, and simultaneous determination of orthophosphate, pyrophosphate, and tripolyphosphate by capillary electrophoresis with capacitively coupled contactless conductivity detection.

This work describes a novel analytical method using capillary electrophoresis (CE) with capacitively coupled contactless conductivity detection (C4D) for simultaneous, simple, and rapid determination of three inorganic phosphates (orthophosphate, pyrophosphate, and tripolyphosphate) widely used as food additives and in pharmaceutical formulations. A background electrolyte composed of 0.5 mol L-1 acetic acid provided fast separation (around 3.0 min) and good separation efficiency and peak resolution. Linearity in the concentration range of 10-500 mg L-1 was confirmed by the coefficients of determination (R2) higher than 0.99. The limits of detection varied from 0.41 to 0.58 mg L-1. The accuracy of the proposed method was assessed by recovery tests conducted at three concentration levels in tap water samples, food, and personal hygiene products. Recovery values varying from 81% to 118% were achieved, indicating an acceptable accuracy. The proposed CE-C4D successfully determined the three inorganic phosphates in the analyzed samples.

Food-derived peptides unleashed: emerging roles as food additives beyond bioactivities.

Innovating food additives stands as a cornerstone for the sustainable evolution of future food systems. Peptides derived from food proteins exhibit a rich array of physicochemical and biological attributes crucial for preserving the appearance, flavor, texture, and nutritional integrity of foods. Leveraging these peptides as raw materials holds great promise for the development of novel food additives. While numerous studies underscore the potential of peptides as food additives, existing reviews predominantly focus on their biotic applications, leaving a notable gap in the discourse around their abiotic functionalities, such as their physicochemical properties. Addressing this gap, this review offers a comprehensive survey of peptide-derived food additives in food systems, accentuating the application of peptides' abiotic properties. It furnishes a thorough exploration of the underlying mechanisms and diverse applications of peptide-derived food additives, while also delineating the challenges encountered and prospects for future applications. This well-time review will set the stage for a deeper understanding of peptide-derived food additives.

What if gastrointestinal complications in endurance athletes were gut injuries in response to a high consumption of ultra-processed foods? Please take care of your bugs if you want to improve endurance performance: a narrative review.

To improve performance and recovery faster, athletes are advised to eat more often than usual and consume higher doses of simple carbohydrates, during and after exercise. Sports energetic supplements contain food additives, such as artificial sweeteners, emulsifiers, acidity regulators, preservatives, and salts, which could be harmful to the gut microbiota and impair the intestinal barrier function. The intestinal barrier plays a critical function in bidirectionally regulation of the selective transfer of nutrients, water, and electrolytes, while preventing at the same time, the entrance of harmful substances (selective permeability). The gut microbiota helps to the host to regulate intestinal homeostasis through metabolic, protective, and immune functions. Globally, the gut health is essential to maintain systemic homeostasis in athletes, and to ensure proper digestion, metabolization, and substrate absorption. Gastrointestinal complaints are an important cause of underperformance and dropout during endurance events. These complications are directly related to the loss of gut equilibrium, mainly linked to microbiota dysbiosis and leaky gut. In summary, athletes must be cautious with the elevated intake of ultra-processed foods and specifically those contained on sports nutrition supplements. This review points out the specific nutritional interventions that should be implemented and/or discontinued depending on individual gut functionality.

A Survey on Nutrition Labeling for Sodium, Potassium, and Phosphorus of Packaged Food and Beverages.

OBJECTIVES: Nutrition labeling is important to guide patients with chronic kidney disease to make informed choices. This study aimed to evaluate the extent and accessibility of nutrition labeling for sodium, potassium, and phosphorus on food and beverage products in a supermarket. METHODS: A cross-sectional survey was conducted in a Malaysian supermarket. Information on sodium, potassium, and phosphorus contents was collected from the nutrition fact panel, while information on food additives containing sodium, potassium, and phosphorus was collected from the ingredient list. RESULTS: The survey included 2,577 foods and beverages, and 79.4% of the products included sodium information in nutrition fact panels, but only 11.7% and 2.0% disclosed potassium and phosphorus content, respectively. Sodium-containing additives were found in 78.6% of products; potassium- and phosphorus-containing additives were reported in 28.5% and 46.9% of products, respectively. Sodium-containing additives were typically listed as "salt," potassium-containing additives as "alternative names," and phosphorus-containing additives as "starch" and "E numbers." Imported products were more likely to include sodium (P < .001) and phosphorus (p = .036) contents, while more locally manufactured products reported sodium- (p = .003) and phosphorus- (P = .004) containing additives. CONCLUSION: There is limited availability of potassium and phosphorus information on nutrition labels in Malaysia food and beverage products, which presents significant challenges for individuals with chronic kidney disease in choosing appropriate products for their dietary needs.

Highly flexible copper tape decorated with Ag nanoarrays as ultrasensitive SERS platforms for multi-hazardous pollutant sensing.

A highly flexible and cost-effective copper tape decorated with silver nanoparticles (Cu-TAg) has been developed for surface-enhanced Raman spectroscopy (SERS) sensing of multi-hazardous environmental pollutants. Highly ordered and spherical-shaped silver nanoarrays have been fabricated using a low-cost thermal evaporation method. The structural, morphological, and optical properties of Cu-TAg sensors have been studied and correlated to the corresponding SERS performances. The size of nanoparticles has been successively tuned by varying the deposition time from 5 to 25 s. The nanoparticle sizes were enhanced with an increase in the evaporation time. SERS investigations have revealed that the sensing potential is subsequently improved with an increase in deposition time up to 10 s and then deteriorates with further increase in Ag deposition. The highest SERS activity was acquired for an optimum size of ~ 37 nm; further simulation studies confirmed this observation. Moreover, Cu-TAg sensors exhibited high sensitivity, reproducibility, and recycling characteristics to be used as excellent chemo-sensors. The lower detection limit estimation revealed that it can sense even in the pico-molar range for sensing of rhodamine 6G and methylene blue. The estimated enhancement factor of the sensor is found to be 9.4 × 107. Molecular-specific sensing of a wide range of pollutants such as rhodamine 6G, alizarin red, methylene blue, butylated hydroxy anisole, and penicillin-streptomycin is demonstrated with high efficiencies for micromolar spiked samples. Copper tape functionalized with Ag arrays thus demonstrated to be a promising candidate for low-cost and reusable chemo-sensors for environmental remediation applications.

A comprehensive review of the application of Zr-based metal-organic frameworks for electrochemical sensors and biosensors.

A family of inorganic-organic hybrid crystalline materials made up of organic ligands and metal cations or clusters is known as metal-organic frameworks (MOFs). Because of their unique stability, intriguing characteristics, and structural diversity, zirconium-based MOFs (Zr-MOFs) are regarded as one of the most interesting families of MOF materials for real-world applications. Zr-MOFs that have the ligands, metal nodes, and guest molecules enclosed show distinct electrochemical reactions. They can successfully and sensitively identify a wide range of substances, which is important for both environmental preservation and human health. The rational design and synthesis of Zr-MOF electrochemical sensors and biosensors, as well as their applications in the detection of drugs, biomarkers, pesticides, food additives, hydrogen peroxide, and other materials, are the main topics of this comprehensive review. We also touch on the current issues and potential future paths for Zr-MOF electrochemical sensor research.

Oral Excretion Kinetics of Food-Additive Silicon Dioxides and Their Effect on In Vivo Macrophage Activation.

A food additive, silicon dioxide (SiO2) is commonly used in the food industry as an anti-caking agent. The presence of nanoparticles (NPs) in commercial food-grade SiO2 has raised concerns regarding their potential toxicity related to nano size. While recent studies have demonstrated the oral absorption and tissue distribution of food-additive SiO2 particles, limited information is available about their excretion behaviors and potential impact on macrophage activation. In this study, the excretion kinetics of two differently manufactured (fumed and precipitated) SiO2 particles were evaluated following repeated oral administration to rats for 28 d. The excretion fate of their intact particles, decomposed forms, or ionic forms was investigated in feces and urine, respectively. Monocyte uptake, Kupffer cell activation, and cytokine release were assessed after the oral administration of SiO2 particles. Additionally, their intracellular fates were determined in Raw 264.7 cells. The results revealed that the majority of SiO2 particles were not absorbed but directly excreted via feces in intact particle forms. Only a small portion of SiO2 was eliminated via urine, predominantly in the form of bioconverted silicic acid and slightly decomposed ionic forms. SiO2 particles were mainly present in particle forms inside cells, followed by ionic and silicic acid forms, indicating their slow conversion into silicic acid after cellular uptake. No effects of the manufacturing method were observed on excretion and fates. Moreover, no in vivo monocyte uptake, Kupffer cell polarization, or cytokine release were induced by orally administered SiO2 particles. These finding contribute to understanding the oral toxicokinetics of food-additive SiO2 and provide valuable insights into its potential toxicity.

Auricularia auricula Anionic Polysaccharide Nanoparticles for Gastrointestinal Delivery of Pinus koraiensis Polyphenol Used in Bone Protection under Weightlessness.

Auricularia auricula polysaccharides used in Pinus koraiensis polyphenol encapsulation and delivery under weightlessness are rarely reported. In this study, an anionic polysaccharide fragment named AAP Iα with a molecular weight of 133.304 kDa was isolated and purified to construct a polyphenol encapsulation system. Nanoparticles named NPs-PP loaded with a rough surface for Pinus koraiensis polyphenol (PP) delivery were fabricated by AAP Iα and ε-poly-L-lysine (ε-PL). SEM and the DLS tracking method were used to observe continuous changes in AAP Iα, ε-PL and PP on the nanoparticles' rough surface assembly, as well as the dispersion and stability. Hydrophilic, monodisperse and highly negative charged nanoparticles can be formed at AAP Iα 0.8 mg/mL, ε-PL 20 µg/mL and PP 80 µg/mL. FT-IR was used to determine their electrostatic interactions. Release kinetic studies showed that nanoparticles had an ideal gastrointestinal delivery effect. NPs-PP loaded were assembled through electrostatic interactions between polyelectrolytes after hydrogen bonding formation in PP-AAP Iα and PP-ε-PL, respectively. Colon adhesion properties and PP delivery in vivo of nanoparticles showed that NPs-PP loaded had high adhesion efficiency to the colonic mucosa under simulated microgravity and could enhance PP bioavailability. These results suggest that AAP Iα can be used in PP encapsulation and delivery under microgravity in astronaut food additives.

Dysregulated phosphate metabolism in autism spectrum disorder: associations and insights for future research.

Studies of autism spectrum disorder (ASD) related to exposure to toxic levels of dietary phosphate are lacking. Phosphate toxicity from dysregulated phosphate metabolism can negatively impact almost every major organ system of the body, including the central nervous system. The present paper used a grounded theory-literature review method to synthesise associations of dysregulated phosphate metabolism with the aetiology of ASD. Cell signalling in autism has been linked to an altered balance between phosphoinositide kinases, which phosphorylate proteins, and the counteracting effect of phosphatases in neuronal membranes. Glial cell overgrowth in the developing ASD brain can lead to disturbances in neuro-circuitry, neuroinflammation and immune responses which are potentially related to excessive inorganic phosphate. The rise in ASD prevalence has been suggested to originate in changes to the gut microbiome from increasing consumption of additives in processed food, including phosphate additives. Ketogenic diets and dietary patterns that eliminate casein also reduce phosphate intake, which may account for many of the suggested benefits of these diets in children with ASD. Dysregulated phosphate metabolism is causatively linked to comorbid conditions associated with ASD such as cancer, tuberous sclerosis, mitochondrial dysfunction, diabetes, epilepsy, obesity, chronic kidney disease, tauopathy, cardiovascular disease and bone mineral disorders. Associations and proposals presented in this paper offer novel insights and directions for future research linking the aetiology of ASD with dysregulated phosphate metabolism and phosphate toxicity from excessive dietary phosphorus intake.

3D printing technology for prepared dishes: printing characteristics, applications, challenges and prospects.

Prepared dishes are popular convenience foods that meet the needs of consumers who pursue delicious tastes while saving time and effort. As a new technology, food 3D printing (also known as food additive manufacturing technology) has great advantage in the production of personalized food. Applying food 3D printing technology in the production of prepared dishes provides the solution to microbial contamination, poor nutritional quality and product standardization. This review summarizes the problems faced by the prepared dishes industry in traditional food processing, and introduces the characteristics of prepared dishes and 3D printing technology. Food additives are suitable for 3D prepared dishes and novel 3D printing technologies are also included in this review. In addition, the challenges and possible solutions of the application of food 3D printing technology in the field of prepared dishes are summarized and explored. Food additives with advantages in heat stability, low temperature protection and bacteriostasis help to accelerate the application of 3D printing in prepared dishes industry. The combination of 3D printing technology with heat-assisted sources (microwave, laser) and non-heat-assisted sources (electrolysis, ultrasound) provides the possibility for the development of customized prepared dishes in the future, and also promotes more 3D food printing technologies for commercial use. It is noteworthy that these technologies are still at research stage, and there are challenges for the formulation design, the stability of printed ink storage, as well as implementation of customized nutrition for the elderly and children.

Novel insight into the role of sulfur dioxide in fruits and vegetables: Chemical interactions, biological activity, metabolism, applications, and safety.

Sulfur dioxide (SO2) are a category of chemical compounds widely used as additives in food industry. So far, the use of SO2 in fruit and vegetable industry has been indispensable although its safety concerns have been controversial. This article comprehensively reviews the chemical interactions of SO2 with the components of fruit and vegetable products, elaborates its mechanism of antimicrobial, anti-browning, and antioxidation, discusses its roles in regulation of sulfur metabolism, reactive oxygen species (ROS)/redox, resistance induction, and quality maintenance in fruits and vegetables, summarizes the application technology of SO2 and its safety in human (absorption, metabolism, toxicity, regulation), and emphasizes the intrinsic metabolism of SO2 and its consequences for the postharvest physiology and safety of fresh fruits and vegetables. In order to fully understand the benefits and risks of SO2, more research is needed to evaluate the molecular mechanisms of SO2 metabolism in the cells and tissues of fruits and vegetables, and to uncover the interaction mechanisms between SO2 and the components of fruits and vegetables as well as the efficacy and safety of bound SO2. This review has important guiding significance for adjusting an applicable definition of maximum residue limit of SO2 in food.

Consumption of low-calorie sweeteners: findings from the Campinas Nutrition and Health Survey.

We used data from the Campinas Health Survey (ISACamp 2014/15) and the Food Consumption and Nutritional Status Survey (ISACamp-Nutri 2015/16) to estimate the prevalence of the consumption of foods and beverages that contain low-calorie sweeteners (LCS) by individuals ≥ 10 years to estimate the dietary exposure of the population to high levels of LCS. We first estimated the prevalence of consuming LCS-containing foods and beverages and identified the top sources of LCS consumption. We then verified whether the prevalence of consumption varied according to individual-level characteristics or the presence of obesity and diabetes. Finally, we estimated the population dietary exposure to high levels of LCS and compared it with the acceptable daily intake (ADI) levels. Over 40 % of the study population consumed at least one LCS-containing food or beverage. Sweetened beverages, tabletop sweeteners and dairy beverages were the top contributors to the consumption of LCS. Among all age groups, education levels, and income levels, the consumption of LCS-containing foods and beverages ranged from 35 % to 55 %. The prevalence was only slightly greater among higher income 40-59-year-olds than among other income groups and was not higher among individuals with obesity or diabetes. Although dietary exposure to LCS did not exceed the ADI levels, we identified several limitations in our ability to measure exposure to high levels of LCS. Because of these challenges and the unclear evidence linking LCS to better health outcomes, the consumption of LCS-containing foods and beverages should be closely monitored.

The nutritional profile of commercial complementary foods in Japan: comparison between low- and high-price products.

Despite the increasing market share of commercial complementary foods, their nutritional characteristics and those associated with the price of products are still unknown in Japan. We compared the nutritional characteristics of commercially available complementary foods of different price levels in Japan. Data were obtained from the websites of Japanese brands of infant and young children's food. Nutrient profiles (unit/100 g), ingredients and food additives were compared between low- and high-priced products by product type. Sixty-three dry meals, 425 soft meals, 187 snacks and sweets, and 60 drinks were analysed. One-fifth of meals and snacks exceeded the CODEX-defined limit (200 mg Na/100 g). Most products lacked content information on nutrients non-mandated to be indicated. High-priced soft meals contained more protein (2·5 v. 1·9 g/100 g) and less Na (0·18 v. 0·46 g/100 g), less frequently used ≥ 1 added sugar (23 % v. 82 %), and less frequently used food additives than low-priced products; however, they had a lower variety of ingredients. The prevalence of products containing ≥ 1 added sugar was higher in low-priced snacks and sweets (91 % v. 77 %) but lower in drinks (48 % v. 84 %) than in their high-priced counterparts. High Na content is a concern among commercial complementary foods in Japan. Nonetheless, the relationship between the price and nutritional profile of these foods differs by product type. High-priced soft meals might be more favourable regarding nutrient content but not the variety of ingredients than low-priced counterparts. These findings elucidate the nutritional characteristics of commercial complementary foods in Japan.

Insights into the Occurrence, Fate, Impacts, and Control of Food Additives in Food Waste Anaerobic Digestion: A Review.

The recovery of biomass energy from food waste through anaerobic digestion as an alternative to fossil energy is of great significance for the development of environmental sustainability and the circular economy. However, a substantial number of food additives (e.g., salt, allicin, capsaicin, allyl isothiocyanate, monosodium glutamate, and nonnutritive sweeteners) are present in food waste, and their interactions with anaerobic digestion might affect energy recovery, which is typically overlooked. This work describes the current understanding of the occurrence and fate of food additives in anaerobic digestion of food waste. The biotransformation pathways of food additives during anaerobic digestion are well discussed. In addition, important discoveries in the effects and underlying mechanisms of food additives on anaerobic digestion are reviewed. The results showed that most of the food additives had negative effects on anaerobic digestion by deactivating functional enzymes, thus inhibiting methane production. By reviewing the response of microbial communities to food additives, we can further improve our understanding of the impact of food additives on anaerobic digestion. Intriguingly, the possibility that food additives may promote the spread of antibiotic resistance genes, and thus threaten ecology and public health, is highlighted. Furthermore, strategies for mitigating the effects of food additives on anaerobic digestion are outlined in terms of optimal operation conditions, effectiveness, and reaction mechanisms, among which chemical methods have been widely used and are effective in promoting the degradation of food additives and increasing methane production. This review aims to advance our understanding of the fate and impact of food additives in anaerobic digestion and to spark novel research ideas for optimizing anaerobic digestion of organic solid waste.

Determination of Monosodium Glutamate in Noodles Using a Simple Spectrofluorometric Method based on an Emission Turn-on Approach.

A simple, fast, and ecofriendly spectrofluorometric method was developed and validated for determination of mono sodium glutamate (MSG). The method depended on the reaction between MSG and iron (III) salicylate based on ligand exchange mechanism. Addition of MSG turned-on the fluorescent response of iron (III) salicylate at λem 411 nm. Reaction conditions including reagent concentration, pH, and time were optimized. The method was validated regarding the ICH guidelines. The method determined MSG within the linearity range of 25-250 µM with a coefficient of determination of 0.9967 and a calculated limit of detection of 1.73 µM. Furthermore, the developed method was successfully applied for the determination of MSG in food preparation (instant noodles). The results were compared to those obtained by a published HPLC method using t-test and F-test at 95% confidence interval; no statistically significant difference was found. Based on the analytical Eco-scale and the green analytical procedure index (GAPI), the developed method was assessed to be greener than the published HPLC method. The developed method offered advantages over other spectrophotometric reported methods and was convenient for routine determination of MSG in foodstuffs.

Children With Celiac Disease Consume Specific Food Additives More Frequently Compared to Children Without Celiac Disease.

BACKGROUND: Gluten-free foods often contain food additives to improve palatability, but the long-term effects on the human gastrointestinal tract are not well known. AIMS: This study aimed to quantify frequency of food additive exposure in children with and without celiac disease (CD). METHODS: Children with and without CD were enrolled and demographic data and three-day diet records were obtained. Foods were classified as gluten-free products (GFP) and "processed food", and were evaluated for presence of select food additives: polysorbate 80, carboxymethylcellulose, xanthan gum, guar gum, soy lecithin, titanium dioxide, carrageenan, maltodextrin, and aluminosilicates. The frequency of exposure was described. RESULTS: Twenty-eight participants were included in final analysis. Children with CD had a higher number of daily exposures to xanthan gum (5.3 ± 3.1 vs 2.3 ± 2.4; p = 0.009), but similar exposures to the other additives. GFP contributed 29% of total calories in the GF diet. Both groups had similar intake of processed foods. Comparing GFP and gluten-containing processed foods, 68% vs. 25% contained at least one food additive of interest (p < 0.0001); in the celiac group, those with higher consumption of GFP tended to have a higher frequency of exposure to food additives (p = 0.09). CONCLUSION: A gluten-free diet and consumption of GFP may contribute to differences in food additive intake; quantifying food additive exposures and their effect on humans requires further study.

A mixture of 13 pesticides, contaminants, and food additives below individual NOAELs produces histopathological and organ weight changes in rats.

The current approach for the risk assessment of chemicals does not account for the complex human real-life exposure scenarios. Exposure to chemical mixtures in everyday life has raised scientific, regulatory, and societal concerns in recent years. Several studies aiming to identify the safety limits of chemical mixtures determined hazardous levels lower than those of separate chemicals. Following these observations, this study built on the standards set by the real-life risk simulation (RLRS) scenario and investigated the effect of long-term exposure (18 months) to a mixture of 13 chemicals (methomyl, triadimefon, dimethoate, glyphosate, carbaryl, methyl parathion, aspartame, sodium benzoate, EDTA, ethylparaben, butylparaben, bisphenol A and acacia gum) in adult rats. Animals were divided into four dosing groups [0xNOAEL (control), 0.0025xNOAEL (low dose-LD), 0.01xNOAEL (medium dose-MD) and 0.05xNOAEL (high dose-HD) (mg/kg BW/day)]. After 18 months of exposure, all animals were sacrificed, and their organs were harvested, weighed, and pathologically examined. While organ weight tended to be higher in males than in females, when sex and dose were taken into account, lungs and hearts from female rats had significantly greater weight than that of males. This discrepancy was more obvious in the LD group. Histopathology showed that long-term exposure to the chemical mixture selected for this study caused dose-dependent changes in all examined organs. The main organs that contribute to chemical biotransformation and clearance (liver, kidneys, and lungs) consistently presented histopathological changes following exposure to the chemical mixture. In conclusion, exposure to very low doses (below the NOAEL) of the tested mixture for 18 months induced histopathological lesions and cytotoxic effects in a dose and tissue-dependent manner.

Flavour, emulsifiers and colour are the most frequent markers to detect food ultra-processing in a UK food market analysis.

OBJECTIVE: To elucidate which markers of ultra-processing (MUP) and their combinations are best suited to detect ultra-processed food (UPF). DESIGN: The study was based on the 206 food and 32 beverage items of the Oxford WebQ which encompass all major foods consumed in the UK. For each Oxford WebQ question, ingredient lists of up to ten matching different commercial products (n 2146) were researched online using data from the two market leaders of groceries in the UK sorted by relevance (Tesco) and by top sellers (Sainsbury's), respectively. According to the NOVA classification, sixty-five MUP were defined, and if the ingredient list of a food product was positive for at least one MUP, it was regarded as UPF. The percentage of UPF items containing specific MUP was calculated. In addition, all combinations of two to six different MUP were assessed concerning the percentage of identified UPF items. SETTING: Cross-sectional analysis. PARTICIPANTS: None. RESULTS: A total of 990 products contained at least one MUP and were, therefore, regarded as UPF. The most frequent MUP were flavour (578 items, 58·4 % of all UPF), emulsifiers (353 items, 35·7 % of all UPF) and colour (262 items, 26·5 % of all UPF). Combined, these three MUP detected 79·2 % of all UPF products. Detection rate increased to 88·4 % of all UPF if ingredient lists were analysed concerning three additional MUP, that is, fibre, dextrose and firming agent. CONCLUSIONS: Almost 90 % of all UPF items can be detected by six MUP.

In vitro and in vivo acute toxicity of an artificial butter flavoring.

Flavorings used in cookies, electronic cigarettes, popcorn, and breads contain approximately 30 chemical compounds, which makes it difficult to determine and correlate signs and symptoms of acute, subacute or chronic toxicity. The aim of this study was to characterize a butter flavoring chemically and subsequently examine the in vitro and in vivo toxicological profile using cellular techniques, invertebrates, and lab mammals. For the first time, the ethyl butanoate was found as the main compound of a butter flavoring (97.75%) and 24 h-toxicity assay employing Artemia salina larvae revealed a linear effect and LC50 value of 14.7 (13.7-15.7) mg/ml (R2 = 0.9448). Previous reports about higher oral doses of ethyl butanoate were not found. Observational screening with doses between 150-1000 mg/kg by gavage displayed increased amount of defecation, palpebral ptosis, and grip strength reduction, predominantly at higher doses. The flavoring also produced clinical signs of toxicity and diazepam-like behavioral changes in mice, including loss of motor coordination, muscle relaxation, increase of locomotor activity and intestinal motility, and induction of diarrhea, with deaths occurring after 48 h exposure. This substance fits into category 3 of the Globally Harmonized System. Data demonstrated that butter flavoring altered the emotional state in Swiss mice and disrupted intestinal motility, which may be a result of neurochemical changes or direct lesions in the central/peripheral nervous systems.

Retrospective analysis of dog study data from food and color additive petitions.

As part of the US FDA CFSAN's efforts to explore alternatives to animal testing, we retrospectively analyzed a sample of food additive (FAP) and color additive petitions (CAP) submitted to the FDA for the utility of dog study data in safety assessment. FAPs and CAPs containing dog studies (161 petitions) were classified as decisive (38%), supportive (27%), supplemental (29%) or undermined (6%) based on the impact the dog study data had on the final safety decision. Petitions classified as decisive were further categorized based on if the dog study data were used to a) address a safety concern (35/61); b) calculate an acceptable daily intake (ADI) (11/61); c) withdraw a petition (4/61); d) the effect was unique to the dog (2/61); or e) unclear (9/61). Of 11 petitions where the dog study was used to set an ADI, 7 contained studies where the points of departure (POD) from the dog studies were within an 8-fold range of the rodent with differences in study design likely contributing to the difference in PODs. Future research should include the development and use of qualified alternative studies to replace the use of animal testing for food and color additive safety assessment while ensuring human safety.