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Erythrosine, a synthetic food dye, has been controversial due to its potential health risks. This study examines the effect of erythrosine on activity of antioxidative enzymes, oxidative stress indices, DNA damage through comet assay, and histopathological changes on stomach, intestine, and colon over a period of 28 days in rats. Twenty-four rats were randomly divided into four groups (n = 6). The first is the control group and then one each for three doses of erythrosine based on acceptable daily intake (¼ ADI, ½ ADI, and ADI, 0.1 mg/kg body weight). The results revealed that with increasing dosages the activity of catalase decreased in stomach and intestine but in colon, the catalase activity increased. Superoxide dismutase and glutathione-S-transferase activity decreased in dose-dependent manner in all three tissues. While, in stomach and intestine, the acetylcholinesterase activity showed increment in ¼ ADI dose group and then declined in ½ ADI and ADI dose-administered rats. The oxidative stress indicators showed elevated levels of lipid peroxidation, hydrogen peroxide concentration, and lactate dehydrogenase activity suggesting heightened free radical activity and potential oxidative damage. The comet test was used to evaluate DNA damage, revealing substantial damage in the erythrosine administered groups. Histopathological examination showed inflammatory infiltration and other degenerative changes in gastrointestinal tract, highlighting the dye's adverse effects. The research underscores the need for a comprehensive reevaluation of the safety and toxicity of food dyes like erythrosine, especially considering the inconsistencies in existing studies regarding the dye's safety., (© 2024 Wiley Periodicals LLC.)

Many additives, some of which have no nutritional value, can be legally used in processed foods. They intensify colour, thicken, increase shelf life and enhance flavour. Regulatory authorities issue approvals as safe within acceptable quantitative limits. Ultra-processed foods (UPFs) contain combinations of all these additives and are particularly attractive to children.Many publications suggest that artificial colourants, benzoate preservatives, non-caloric sweeteners, emulsifiers and their degradation derivatives have adverse effects by increasing risks of mental health disorders, attention deficit hyperactivity disorder, cardiovascular disease, metabolic syndrome and potential carcinogenic effects.A systematic review has established that artificial azo dye food colourants (AFCs) and sodium benzoate preservative cause disturbed behaviour in children. AFCs and benzoates in animal models have neurotoxic properties through gut microbial generation of toxic metabolites. Observational studies show associations between high emulsifier intake and cardiovascular disease. Animal models and in vitro studies have highlighted neurotoxic, cytotoxic, genotoxic and carcinogenic effects. High intake of non-caloric sweeteners has been linked to cardiovascular disease and depression in adults and is linked to childhood obesity.Little research has focused on children who are the largest consumers of UPFs. Potentially, they are a ticking time bomb for adult obesity, metabolic syndrome, cardiovascular diseases, mental health disorders and cancers. Based on risk/benefit analysis, azo dye AFCs should be banned. Benzoates, emulsifiers and sweeteners require assessment of quantitative limits and cumulative effects of combinations. Consumers purchasing UPFs require information through ingredient health warnings and recommendations to use natural unprocessed foods which have well-described health-promoting properties., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Merriam-Webster and Oxford define a xenobiotic as any substance foreign to living systems. Allura Red AC (a.k.a., E129; FD&C Red No. 40), a synthetic food dye extensively used in manufacturing ultra-processed foods and therefore highly prevalent in our food supply, falls under this category. The surge in synthetic food dye consumption during the 70s and 80s was followed by an epidemic of metabolic diseases and the emergence of early-onset colorectal cancer in the 1990s. This temporal association raises significant concerns, particularly given the widespread inclusion of synthetic food dyes in ultra-processed products, notably those marketed toward children. Given its interactions with key contributors to colorectal carcinogenesis such as inflammatory mediators, the microbiome, and DNA damage, there is growing interest in understanding Allura Red AC's potential impact on colon health as a putative carcinogen. This review discusses the history of Allura Red AC, current research on its effects on the colon and rectum, potential mechanisms underlying its impact on colon health, and provides future considerations. Indeed, although no governing agencies classify Allura Red AC as a carcinogen, its interaction with key guardians of carcinogenesis makes it suspect and worthy of further molecular investigation. The goal of this review is to inspire research into the impact of synthetic food dyes on colon health., (© The Author(s) 2024. Published by Oxford University Press.)

This study addressed the harmful effects of artificial colors in pediatric populations, including children diagnosed with Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD), as well as those without behavioral disorders. There is a consensus that synthetic food colorings have several impacts on consumers, especially pediatrics, due to their influence on sensory appeal, which can encourage preference for certain foods. The results revealed that these color additives are directly linked to a series of health problems, with a greater impact on children, including a predisposition to pathological conditions such as carcinogenic, allergenic, mutagenic, cytotoxic, and clastogenic activities, as well as gastrointestinal and respiratory problems, in addition to behavioral changes in children with and without diagnosed disorders. The harms of synthetic dyes in children with or without comorbidities are worrying and require a careful and proactive approach from parents, caregivers and public authorities.

Background: In today's world, appearance is an important factor in almost all areas of our lives. Therefore, it has become common to use dyes to color foods to make them look appetizing and visually appealing. However, food additives have negative effects on biochemical processes in cells at both high and low doses., Methods and Results: This study investigated the effect of carmoisine, a commonly used food coloring, on oxidative stress and damage parameters in Drosophila melanogaster in terms of both enzymatic and gene expression. The change in mitochondrial DNA copy number (mtDNA-CN), a marker of oxidative stress, was also examined. When the data obtained were analyzed, it was observed that carmoisine caused a significant decrease in GSH levels depending on the increase in dose. SOD, CAT, GPx, and AChE enzyme activities and gene expression levels were also found to be significantly decreased. All groups also showed a significant decrease in mtDNA-CN. The effect of carmoisine on Drosophila melanogaster morphology was also investigated in our study. However, no significant change was observed in terms of morphological development in any group., Conclusions: When all the findings were evaluated together, it was observed that carmoisin triggered oxidative stress and these effects became more risky at high doses. Therefore, we believe that the consumer should be made more aware of the side effects of azo dyes in food and that the type and concentration of each substance added to food should be specified., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

In recent years, artificial additives, especially synthetic food colorants, were found to demonstrate wider properties compared to their natural equivalents; however, their health impact is still not totally mapped. Our study aimed to determine the long-term (30 and 90 days) exposure effect of one of the commonly used artificial food colorants, tartrazine, on NMRI mice. The applied dose of tartrazine referred to the human equivalent dose for acceptable daily intake (ADI). Further, we evaluated its impact on the transcription of a range of epigenetic effectors, members of the DNA methyltransferase ( DNMT ) as well as histone deacetylase ( HDAC) families. Following the exposure, organ biopsies were collected from the lungs, kidneys, liver, and spleen, and the gene expression levels were determined by real-time quantitative reverse transcription PCR (RT-qPCR). Our results demonstrated significant upregulation of genes in the tested organs in various patterns followed by the intake of tartrazine on ADI. Since DNMT and HDAC genes are involved in different steps of carcinogenesis, have roles in the development of neurological disorders and the effect of dose of everyday exposure is rarely studied, further investigation is warranted to study these possible associations.

Food color additives are used to make food more appetizing. The United States Food and Drug Administration (FDA) permitted nine artificial colorings in foods, drugs, and cosmetics, whereas the European Union (EU) approved five artificial colors (E-104, 122, 124, 131, and 142) for food. However, these synthetic coloring materials raise various health hazards. The present review aimed to summarize the toxic effects of these coloring food additives on the brain, liver, kidney, lungs, urinary bladder, and thyroid gland. In this respect, we aimed to highlight the scientific evidence and the crucial need to assess potential health hazards of all colors used in food on human and nonhuman biota for better scrutiny. Blue 1 causes kidney tumor in mice, and there is evidence of death due to ingestion through a feeding tube. Blue 2 and Citrus Red 2 cause brain and urinary bladder tumors, respectively, whereas other coloring additives may cause different types of cancers and numerous adverse health effects. In light of this, this review focuses on the different possible adverse health effects caused by these food coloring additives, and possible ways to mitigate or avoid the damage they may cause. We hope that the data collected from in vitro or in vivo studies and from clinical investigations related to the possible health hazards of food color additives will be helpful to both researchers and the food industry in the future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The food colorant Red 40 is an environmental risk factor for colitis development in mice with increased expression of interleukin (IL)-23. This immune response is mediated by CD4 + T cells, but mechanistic insights into how these CD4 + T cells trigger and perpetuate colitis have remained elusive. Here, using single-cell transcriptomic analysis, we found that several CD4 + T-cell subsets are present in the intestines of colitic mice, including an interferon (IFN)-γ-producing subset. In vivo challenge of primed mice with Red 40 promoted rapid activation of CD4 + T cells and caused marked intestinal epithelial cell (IEC) apoptosis that was attenuated by depletion of CD4 + cells and blockade of IFN-γ. Ex vivo experiments showed that intestinal CD4 + T cells from colitic mice directly promoted apoptosis of IECs and intestinal enteroids. CD4 + T cell-mediated cytotoxicity was contact-dependent and required FasL, which promoted caspase-dependent cell death in target IECs. Genetic ablation of IFN-γ constrained IL-23- and Red 40-induced colitis development, and blockade of IFN-γ inhibited epithelial cell death in vivo. These results advance the understanding of the mechanisms regulating colitis development caused by IL-23 and food colorants and identify IFN-γ + cytotoxic CD4 + T cells as a new potential therapeutic target for colitis., (© 2022. The Author(s).)

Objectives: Removing artificial food coloring (AFC) is a common dietary intervention for children with Attention-Deficit/Hyperactivity Disorder (ADHD), but has not been tested in young adults. This pilot study examined the effects of AFC on ADHD symptoms and electroencephalography (EEG) in college students with and without ADHD. Methods: At baseline, control and ADHD participants completed the Adult ADHD Self-Report Scale (ASRS), simple and complex attention measures, and resting-state EEG recordings. ADHD participants ( n  = 18) and a subset of controls (extended control group or EC, n  = 11) avoided AFC in their diet for 2 weeks and then were randomized to a double-blind, placebo-controlled crossover challenge. Subjects received either 225 mg AFC disguised in chocolate cookies or placebo chocolate cookies for 3 days each week, with testing on the third day each week. Baseline comparisons were made using Student's t-test or Wilcoxon rank sum tests and challenge period analyses were run using General Linear Modeling. Results: The ADHD group had significantly greater scores on the ASRS ( p  < 0.001), confirming a symptom differential between groups; however, there were no differences in attentional measures or EEG at baseline. The AFC challenge resulted in an increase in posterior mean gamma power ( p  = 0.05), a decrease in posterior relative alpha power ( p  = 0.04), and a marginal increase in inattentive symptoms ( p  = 0.08) in the ADHD group. There were no effects of AFC in the EC group. Discussion: This study indicates that AFC exposure may affect brainwave activity and ADHD symptoms in college students with ADHD. Larger studies are needed to confirm these findings.

Exposure to artificial food color additives (AFCAs) has been implicated in the etiology of certain childhood hyperactivity and learning disabilities. N-methyl-D-aspartate receptors and alpha-7 nicotinic acetylcholine receptor (α7 nAChR) are involved in learning and memory. We administered a mixture of AFCAs (erythrosine, ponceau 4R, allura red AC, sunset yellow FCF, tartrazine, amaranth, brilliant blue, azorubine, and indigotine) to female rats during gestation to investigate the effects of prenatal exposure to AFCAs on neurobehavior, spatial learning, and memory in their offspring. We also investigated whether AFCAs modulate NR2A, NR2B, and α7 nAChR protein levels in their offsprings' hippocampi. Although spatial learning and memory were not altered, the offspring of rats exposed to AFCAs exhibited decreased motivation and increased despair-related behavior. NR2A and NR2B protein levels were significantly reduced in female offspring in the experimental group ( p  < 0.05), whereas α7 nAChR level was not significantly altered. Our results suggest that prenatal exposure to AFCAs may lead to sex-dependent alterations in glutamatergic signaling which may continue into adolescence.

Carmines (E120) are used worldwide as natural food colouring agents of animal origin, with a widespread application, including yoghurts. Despite being considered safe for human health, carmines are known to cause allergic reactions. Our goal was to evaluate the presence of carmines in different yoghurts with a label declaration of E120, purchased in Portugal, and, for the first time, to assess the human risk. The analytical methodology, recommended by JECFA, was based on acid hydrolysis of the samples followed by spectrophotometric UV-Vis analysis at 494 nm. This methodology allowed for a limit of quantification (LOQ) of 39.0 mg/kg and recovery rates higher than 97.7%. All the samples had carmines at levels above the LOQ, ranging between 43.8 and 193.8 mg/kg, with an average of 125.2 ± 34.5 mg/kg. In total, 8 (26.7%) samples exceeded the European Union (EU) maximum permitted level (MPL) established for carmines in this foodstuff, 150 mg/kg. Solid yoghurts presented higher average levels, 137.2 mg/kg, when compared to liquid samples, 107.2 mg/kg, with a significant statistical difference ( p = 0.0236) being observed. No significant statistical difference was observed between white and private labels, whose average levels were very similar, 125.4 vs 125 mg/kg, respectively. Although some samples were above the allowable values, the estimated daily intake (EDI), designed for the different scenarios of different yoghurt types, did not exceed the established ADI, 5 mg/kg bw/day. According to the obtained results, carmine ingestion through the consumption of yoghurt poses low risk to the Portuguese consumers. However, children were the most vulnerable population group with a calculated risk value of up to 10% considering the mean content scenario. These first findings point out the need to reinforce surveillance programmes and monitoring studies, contributing to an increased awareness regarding carmine exposure, however it must be emphasised that yoghurt has evident nutritional benefits depending on a healthful consumer choice.

Both genetic predisposition and environmental factors appear to play a role in inflammatory bowel disease (IBD) development. Genetic studies in humans have linked the interleukin (IL)-23 signaling pathway with IBD, but the environmental factors contributing to disease have remained elusive. Here, we show that the azo dyes Red 40 and Yellow 6, the most abundant food colorants in the world, can trigger an IBD-like colitis in mice conditionally expressing IL-23, or in two additional animal models in which IL-23 expression was augmented. Increased IL-23 expression led to generation of activated CD4 + T cells that expressed interferon-γ and transferred disease to mice exposed to Red 40. Colitis induction was dependent on the commensal microbiota promoting the azo reduction of Red 40 and generation of a metabolite, 1-amino-2-naphthol-6-sulfonate sodium salt. Together these findings suggest that specific food colorants represent novel risk factors for development of colitis in mice with increased IL-23 signaling., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

California's Office of Environmental Health Hazard Assessment was tasked with conducting risk assessments for United States Food and Drug Administration-approved food dyes relative to neurobehavioral concerns. The purpose of this assessment was to evaluate the evidence for neurodevelopment effects based on three streams of evidence: 1) studies identified by OEHHA for consideration in a quantitative risk assessment; 2) studies relevant to understanding mechanisms of neurobehavioral effects; 3) an in silico assessment of the bioavailability of USFDA-approved food dyes. The results indicate a lack of adequate or consistent evidence of neurological effects, supported by a lack of bioavailability and brain penetration predicted by the in silico assessment. Further, the mechanistic evidence supports a lack of activity from in vitro neurotransmitter assays, and a lack of evidence to support molecular initiating events or key events in adverse outcome pathways associated with neurodevelopmental effects, supporting a lack of biological plausibility for neurobehavioral effects following food exposures to colors. These conclusions are consistent with other authoritative bodies, such as JECFA and EFSA, that have determined (i) other effects are more appropriate for estimating acceptable daily intakes and (ii) evidence from the neurobehavioral studies lack the strength to be relied upon for quantitative risk assessment., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Allergic reactions to food additives are often suspected by families. The aim of this study was to describe oral food challenge (OFC) outcomes in a pediatric cohort with a suspected diagnosis of allergy to food additives (food dyes or sodium benzoate)., Methods: All patients who underwent an open OFC to carmine red, cochineal red, erythrosine, patent blue V, tartrazine, yellow sunset S, and/or sodium benzoate were included. A survey was sent to families after testing to evaluate whether the OFC results had altered feeding behaviors with food additives., Results: Twenty-three patients were included. The main suspected food was candy (n=11/23; 48%). Only one OFC out of 45 was formally positive for the carmine and cochineal red. Subsequently, most OFCs were negative (44/45; 97.8%). Despite the negativity of the challenge, four families out of 14 reported occurrences of supposed allergic reactions to food additives and six out of 15 continued to completely avoid the additive of concern in their children's diet., Conclusions: Allergies to food additives remain rare. Even if an IgE-mediated allergy was excluded with a negative OFC, families remained suspicious about ready-made products. Health professionals and parents should be reassured about the low risk of food dye intolerance or allergies., (Copyright © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Food coloring is often used as a coloring agent in foods, medicines and cosmetics, and it was reported to have certain carcinogenic and mutagenic effects in living organisms. Investigation of physiological parameters using zebrafish is a promising methodology to understand disease biology and drug toxicity for various drug discovery on humans. Zebrafish (Danio rerio) is a well-acknowledged model organism with combining assets such as body transparency, small size, low cost of cultivation, and high genetic homology with humans and is used as a specimen tool for the in-vivo throughput screening approach. In addition, recent advances in microfluidics show a promising alternative for zebrafish manipulation in terms of drug administration and extensive imaging capability. This pilot work highlighted the design and development of a microfluidic detection platform for zebrafish larvae through investigating the effects of food coloring on cardiovascular functionality and pectoral fin swing ability. The zebrafish embryos were exposed to the Cochineal Red and Brilliant Blue FCF pigment solution in a concentration of (0.02‰, 0.2‰) cultured in the laboratory from the embryo stage to hatching and development until 9 days post fertilization (d.p.f.). In addition, zebrafish swimming behaviors in terms of pectoral fin beating towards the toxicity screening were further studied by visualizing the induced flow field. It was evidenced that Cochineal Red pigment at a concentration of 0.2‰ not only significantly affected the zebrafish pectoral fin swing behavior, but also significantly increased the heart rate of juvenile fish. The higher concentration of Brilliant Blue FCF pigment (0.2%) increased heart rate during early embryonic stages of zebrafish. However, zebrafish exposed to food coloring did not show any significant changes in cardiac output. The applications of this proposed platform can be further extended towards observing the neurobiological/hydrodynamic behaviors of zebrafish larvae for practical applications in drug tests.

Autism has been increasing dramatically since its description by Leo Kanner in 1943. The Centers for Disease Control and Prevention (CDC) in 2018 has identified 1 in 59 children (1 in 37 boys and 1 in 151 girls) has autism spectrum disorder (ASD). Autistic spectrum disorders and ADHD are complex conditions in which nutritional and environmental factors play major roles. It is important to understand how food can have an impact on their current and future health. Appealing food colors stimulate the consumption of different food products. Since 2011, it is evident that dyes are linked to harmful effects in children. Artificial dyes have neurotoxic chemicals that aggravate mental health problems. Many families with autistic children avoid food dyes in their diet in order to avoid behavioral issues. A study reported that there is a correlation between yellow dye and sleep disturbance. Food colors Blue 1 and 2, Green 3, Red 3, Yellow 5 and 6, Citrus Red 2, and Red 40 can trigger many behaviors in most kids. Artificial food color usually contains petroleum and is manufactured in a chemical process that includes formaldehyde, aniline, hydroxides, and sulfuric acids. Most impurities in the food color are in the form of salts or acids. Sometimes lead, arsenic, and mercury may be present as impurities. The U.S. FDA is yet to study the effects of synthetic dyes on behavior in children. A study conducted at Southampton University in England found a link between food dyes and hyperactive behavior in children. The research does not prove that food coloring actually causes autism spectrum disorder, but there seems to be a link. This chapter attempts to provide a broad review of the available literature on food color and the epidemiology, etiology, prevention, and treatment of autistic spectrum disorder.

Recently, an increased interest in nanotechnology applications can be observed in various fields (medicine, materials science, pharmacy, environmental protection, agriculture etc.). Due to an increasing scope of applications, the exposure of humans to nanoparticles (NPs) is inevitable. A number of studies revealed that after inhalation or oral exposure, NPs accumulate in, among other places, the lungs, alimentary tract, liver, heart, spleen, kidneys and cardiac muscle. In addition, they disturb glucose and lipid homeostasis in mice and rats. In a wide group of nanoparticles currently used on an industrial scale, titanium dioxide nanoparticles-TiO 2 NPs-are particularly popular. Due to their white colour, TiO 2 NPs are commonly used as a food additive (E 171). The possible risk to health after consuming food containing nanoparticles has been poorly explored but it is supposed that the toxicity of nanoparticles depends on their size, morphology, rate of migration and amount consumed. Scientific databases inform that TiO 2 NPs can induce inflammation due to oxidative stress. They can also have a genotoxic effect leading to, among others, apoptosis or chromosomal instability. This paper gives a review of previous studies concerning the effects of exposure to TiO 2 NPs on a living organism (human, animal). This information is necessary in order to demonstrate potential toxicity of inorganic nanoparticles on human health.

Rhodamine B (RhB) is a banned food additive and has been classified as illegal colourant. Therefore, the risk of RhB contamination should be strictly monitored. In this study, a sensitive UPLC-MS/MS method was applied to monitor RhB in 292 various spices such as chilli, pepper and tomato products. The results showed 22.7% of chilli powder samples, 18.5% of pepper powder samples, 11.1% of chilli oil samples and 9.1% of pepper oil samples were contaminated with RhB. Chilli powder contained RhB up to 44,935 μg/kg with an average of 743 μg/kg, pepper powder up to 65.9 μg/kg with an average of 4.1 μg/kg, chilli oil up to 14.6 μg/kg with an average of 1.0 μg/kg and pepper oil up to 1.1 μg/kg with an average of 0.2 μg/kg, respectively. Considering the common consumption of chilli products and pepper products by so many consumers, RhB exposure is significant and should be decreased.

Introduction: Resin composite restorative materials can mimic the natural color and shade of the tooth. However, exogenous colorants from food and drinks can stain them due to adsorption. The influence of Indian food colorants and spices on resin composite restorations has not been evaluated extensively., Aim: This study aims to evaluate the staining capacity of microhybrid and nanohybrid resin-based composites, to saffron extract, tandoori powder, and turmeric powder., Subjects and Methods: Forty samples of microhybrid (Kulzer Charisma) and nanohybrid (3M Filtek Z350) resin composites were prepared using an acrylic template of dimension 5 mm × 3 mm. They were randomly divided into four groups and immersed into solutions of saffron extract, tandoori powder, and turmeric powder. Distilled water was used as the control group. Color values (LFNx01, aFNx01, bFNx01) were measured by colorimeter using the CIE LFNx01aFNx01bFNx01 system before and after 72 h of immersion. Color differences ΔEFNx01ab were statistically analyzed., Statistical Analysis Used: Two-way ANOVA and post-hoc Tukey (honest significant difference) test were done using IBM SPSS Statistics for Windows, Version 19.0. Armonk, NY: IBM Corp., Results and Discussion: : All the immersion media changed the color of the resin composites to varying degrees. However, turmeric solution showed the maximum mean color variation ΔEFNx01ab of 14.8 ± 2.57 in microhybrid resin composites and 16.8 ± 3.50 in nanohybrid resin composites., Conclusion: Microhybrid and nanohybrid resin composites tend to stain to Indian food colorants, especially to turmeric powder., Competing Interests: There are no conflicts of interest

Objectives: The aim of this study was to examine the occurrence of five azo food dyes-tartrazine, sunset yellow, carmoisine, allura red, and ponceau 4 R-in the food supply chain of Singapore and their effects on the in vitro synthesis of leukotriene B 4 (LTB 4 ) and F 2 -isoprostanes., Methods: Trained personnel recorded the names of foods and beverages sold in a local supermarket that contained at least one of the five azo dyes. The occurrence of the azo dyes in the local food supply was computed. The synthesis of LTB 4 and F 2 -isoprostanes from freshly isolated blood neutrophils were measured using gas chromatography-mass spectrometry., Results: Of the 1681 processed food items, 194 (11.54%) contained at least one of the five azo dyes. Tartrazine was most prevalent in food and beverage products sold in Singapore, followed by allura red, sunset yellow, ponceau 4 R, and carmoisine. The five azo dyes augmented the in vitro synthesis of LTB 4 and F 2 -isoprostanes from blood neutrophils. Tartrazine was significantly more potent in increasing LTB 4 synthesis than the other dyes, which exhibited similar potencies. The five food dyes increased the formation of F 2 -isoprostanes from blood neutrophils at all tested concentrations., Conclusion: The high prevalence of azo dyes in the food supply of Singapore and their ability to elicit proinflammatory responses in vitro suggest a potential health risk to the local population., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Caramel color has been used in foods and beverages for over 150 years and is globally regulated as a color additive. The four distinct classes of caramel color (Plain Caramel, Sulfite Caramel, Ammonia Caramel, and Sulfite Ammonia Caramel) are well characterized and each have specifications that take into account processing variables including reactants that can give rise to low molecular weight constituents (e.g., 4-MeI and THI) that may have toxicological significance for evaluating safety. Extensive safety testing has been conducted with the different classes of caramel color and its constituents, including toxicokinetics, genotoxicity, subchronic toxicity, carcinogenicity, and reproductive/developmental toxicity studies. In addition, data is available on uses and use levels that have been used to estimate intakes of caramel colors and their constituents. No Observable Adverse Effect Levels (NOAEL) have been identified for all classes and Acceptable Daily Intakes have been established to ensure safety of use. Available studies support a conclusion that caramel colors are not genotoxic or carcinogenic, and exposure estimates indicate that intake of caramel colors and constituents do not pose undue safety risks. This update summarizes available relevant safety studies and authoritative reviews on caramel colors and its toxicologically important constituents, 4-MeI and THI., (Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.)

The color of food is known to modulate not only consumers' motivation to eat, but also thermal perception. Here we investigated whether the colors of hot soup can influence thermal sensations and body temperature, in addition to the food acceptability and appetite. Twelve young female participants consumed commercial white potage soup, modified to yellow or blue by adding food dyes, at 9 a.m. on 3 separated days. During the test, visual impression (willingness to eat, palatability, comfort, warmth, and anxiety) and thermal sensations were self-reported using visual analog scales. Core (intra-aural) and peripheral (toe) temperatures were continuously recorded 10 min before and 60 min after ingestion. Blue soup significantly decreased willingness to eat, palatability, comfort, and warmth ratings, and significantly increased anxiety feelings compared to the white and yellow soups. After ingestion, the blue soup showed significantly smaller satiety ratings and the tendency of lower thermal sensation scores of the whole body compared to the white and yellow soups. Moreover, a significantly greater increase in toe temperature was found with the yellow soup than the white or blue soup. In conclusion, this study provides new evidence that the colors of hot food may modulate postprandial satiety, thermal sensations and peripheral temperature. Such effects of color may be useful for dietary strategies for individuals who need to control their appetite., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A refined exposure assessment was undertaken to calculate the estimated daily intake (EDI) of the seven FD&C straight-colour additives and five FD&C colour lakes ('synthetic' food colours) approved in the United States. The EDIs were calculated for the US population as a whole and specific age groups, including children aged 2-5 and 6-12 years, adolescents aged 13-18 years, and adults aged 19 or more y. Actual use data were collected from an industry survey of companies that are users of these colour additives in a variety of products, with additional input from food colour manufacturers. Food-consumption data were obtained from the National Health and Nutrition Examination Survey (NHANES). The assessment was further refined by adjusting the intake to more realistic scenarios based on the fraction of products containing colour within specific food categories using data provided by the Mintel International Group Ltd. The results of the analysis indicate that (1) the use levels reported by the industry are consistent with the concentrations measured analytically by the US Food and Drug Administration; and (2) exposure to food-colour additives in the United States by average and high-intake consumers is well below the acceptable daily intake (ADI) of each colour additive as published by the Joint WHO/FAO Committee on Food Additives (JECFA) and allows wide margins of safety. It is concluded that food colour use as currently practised in the United States is safe and does not result in excessive exposure to the population, even at conservative ranges of food consumption and levels of use.

Objective: Synthetic dyes have been reported to exert detrimental effects on the health of humans. This study evaluated the effects of a diet containing tartrazine (Tz) on rats which included: i) biochemical parameters including hepatic enzymes, kidney functions and profiles of lipids; ii) markers of oxidative stress in cells by measuring concentrations of malondialdehyde (MDA) and glutathione (GSH); iii) activities of selected, key hepatic antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx); iv) pathologies of liver. Also, protective effects of three doses of curcumin (CUR), a natural food coloring agent, on these parameters in rats that had been co-exposed to Tz., Materials and Methods: Fifty Wistar male albino rats were randomly divided into five groups: Group I, control, where rats were fed a normal diet; Group II, rats were fed normal diets containing 7.5 mg Tz/kg diet, dry mass (dm); In Groups III, IV and V, rats were fed diets containing Tz plus 1.0, 2.0 or 4.0 g CUR/kg diet, dm, respectively. Whole blood was collected after 90 d of exposure, homogenates of liver were prepared and the above analyses were conducted., Results: Exposure to Tz in the diet caused statistically significant (p<0.05) greater concentrations of lipids, hepatic enzymes, and kidney function parameters as well as the indicator of oxidative stress MDA. Alternatively, activities of several antioxidant enzymes (i.e. CAT, SOD and GPx) and concentration of the substrate GSH, an indicator of non-enzymatic antioxidant capability, were significantly (p<0.05) less than those in control rats not exposed to Tz. Tz caused various histopathological changes in livers of rats, which were characterized by hemorrhage and dilatation of the central vein and sinusoids, hepatocyte necrosis, intracellular vacuolization. Co-administration of 2.0 (Group IV) or 4.0 g CUR/kg diet (Group V) with Tz significantly mitigated effects on functions of liver and kidney and the profile of relative concentrations of lipids. CUR significantly (p<0.05), and almost completely, reversed effects on enzymatic and non-enzymatic antioxidant and indicators of oxidative stress about rats fed Tz (Group II) to values in control rats. However, co-administration of 1.0 g CUR with Tz (Group III) exhibited a negligible effect on those parameters. The results of this study suggest benefits of the use of CUR, as a promising natural food additive to counteract oxidative stress caused by dietary exposure to the synthetic dye Tz due to potent protective antioxidant activity., Conclusions: Blending some natural food additives, such as CUR with diets containing synthetic dyes, could moderate potential effects of these artificial dyes. Decreasing or removing toxins in food is an essential step for the amelioration of human health status and decreasing risk of onset or progression of degenerative diseases.

4-MEI (4-Methylimidazole) is used as a chemical intermediate, crude material or component in the manufacture of pharmaceuticals, photographic and photothermographic chemicals, dyes and pigments and agricultural chemicals. 4-MEI is unintentionally found in our food. Caramel colour (which is the most used beverage colouring and food), dark beers and common brands of cola drinks may comprise more than 100 μg of this compound per 12-ounce serving. 4-MEI is widely used by people and colon cancer is common in our countries. So, it was decided to do in vitro analysis of anti-cancer effect of 4-MEI by MTT test using htc-116 cell line.In this study, mouse Htc-116 cell line was treated with 4-MEI concentrations of 300, 450, 600 and 750 µg/mL for 24 hours and 48 hours periods, after that antiproliferative effect of the 4-MEI was studied by MTT assay. In this study 4-MEI at highest concentration of 24h and at all concentration for 48 h treatment time significantly inhibited cell proliferation when it was compared to control. Also, exposing to the 4-MEI for 48 hours led to a decrease in cells proliferation by concentration dependent manner. This result showed that 4-MEI had anticancer effect in htc-116 cells. However, it has to be evaluated with different new studies (Tab. 1, Fig. 4, Ref. 19).

Dietary exposures to the seven food, drug, and cosmetic (FD&C) colour additives that are approved for general use in food in the United States were estimated for the US population (aged 2 years and older), children (aged 2-5 years) and teenage boys (aged 13-18 years) based on analytical levels of the FD&C colour additives in foods. Approximately 600 foods were chosen for analysis, based on a survey of product labels, for the levels of FD&C colour additives. Dietary exposure was estimated using both 2-day food consumption data from the combined 2007-10 National Health and Nutrition Examination Survey (NHANES) and 10-14-day food consumption data from the 2007-10 NPD Group, Inc. National Eating Trends - Nutrient Intake Database (NPD NET-NID). Dietary exposure was estimated at the mean and 90th percentile using three different exposure scenarios: low exposure, average exposure and high exposure, to account for the range in the amount of each FD&C colour additive for a given food. For all populations and all exposure scenarios, the highest cumulative eaters-only exposures in food were determined for FD&C Red No. 40, FD&C Yellow No. 5 and FD&C Yellow No. 6. In addition, the eaters-only exposure was estimated for individual food categories in order to determine which food categories contributed the most to the exposure for each FD&C colour additive. Breakfast Cereal, Juice Drinks, Soft Drinks, and Frozen Dairy Desserts/Sherbet (also referred to as Ice Cream, Frozen Yogurt, Sherbet (including Bars, Sticks, Sandwiches)) were the major contributing food categories to exposure for multiple FD&C colour additives for all three populations.

Titanium dioxide (TiO₂) nanoparticles are widely used in cosmetics, sunscreens, biomedicine, and food products. When used as a food additive, TiO₂ nanoparticles are used in significant amounts as white food-coloring agents. However, the effects of TiO₂ nanoparticles on the gastrointestinal tract remain unclear. The present study was designed to determine the effects of five TiO₂ particles of different crystal structures and sizes in human epithelial colorectal adenocarcinoma (Caco-2) cells and THP-1 monocyte-derived macrophages. Twenty-four-hour exposure to anatase (primary particle size: 50 and 100 nm) and rutile (50 nm) TiO₂ particles reduced cellular viability in a dose-dependent manner in THP-1 macrophages, but in not Caco-2 cells. However, 72-h exposure of Caco-2 cells to anatase (50 nm) TiO₂ particles reduced cellular viability in a dose-dependent manner. The highest dose (50 µg/mL) of anatase (100 nm), rutile (50 nm), and P25 TiO₂ particles also reduced cellular viability in Caco-2 cells. The production of reactive oxygen species tended to increase in both types of cells, irrespective of the type of TiO₂ particle. Exposure of THP-1 macrophages to 50 µg/mL of anatase (50 nm) TiO₂ particles increased interleukin (IL)-1β expression level, and exposure of Caco-2 cells to 50 µg/mL of anatase (50 nm) TiO₂ particles also increased IL-8 expression. The results indicated that anatase TiO₂ nanoparticles induced inflammatory responses compared with other TiO₂ particles. Further studies are required to determine the in vivo relevance of these findings to avoid the hazards of ingested particles.

Increasing attention has been recently paid to the toxicity of additives used in food. The European Parliament and the Council published the REGULATION (EC) No. 1333/2008 on food additives establishing that the toxicity of food additives evaluated before 20th January 2009 must be re-evaluated by European Food Safety Authority (EFSA). The aim of this review is to survey current knowledge specifically on the toxicity issues of synthetic food colorants using official reports published by the EFSA and other available studies published since the respective report. Synthetic colorants described are Tartrazine, Quinoline Yellow, Sunset Yellow, Azorubine, Ponceau 4R, Erythrosine, Allura Red, Patent Blue, Indigo Carmine, Brilliant Blue FCF, Green S, Brilliant Black and Brown HT. Moreover, a summary of evidence on possible detrimental effects of colorant mixes on children's behaviour is provided and future research directions are outlined., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Positive skin prick test reactions to carmine red (E120) occur in approximately 3% of the patients studied for food allergy. Carmine ingestion associated systemic symptoms are occasionally suspected, but sufficient information of proven carmine allergy is not available., Patients and Methods: To analyse carmine related symptoms in skin prick test positive patients a cohort of 23 patients with suspected allergy to carmine red was subjected to a single-blind placebo-controlled oral challenge test with carmine red., Results: Five patients developed clinical symptoms during the placebo-controlled oral challenge. As a result, the overall frequency of clinical carmine allergy is estimated to be 0.7% in general dermatology patients studied for food-associated symptoms., Conclusions: Oral challenge test provides a valuable in vivo tool to better inform patients with positive skin prick tests to additives to avoid false allergy diets.

Allura Red AC (Food Red No. 40) is a red azo dye that is used for food coloring in beverage and confectionary products. However, its genotoxic properties remain controversial. To clarify the in vivo genotoxicity, we treated mice with Allura Red AC and investigated the induction of DNA damage (liver, glandular stomach), clastogenicity/anuegenicity (bone marrow), and mutagenicity (liver, glandular stomach) using Comet assays, micronucleus tests, and transgenic gene mutation assays, respectively. All studies were conducted in accordance with the Organization for Economic Co-operation and Development (OECD) guideline. Although Allura Red AC was administered up to the maximum doses recommended by the OECD guideline, no genotoxic effect was observed in any of the genotoxic endpoints. These data clearly show no evidence of in vivo genotoxic potential of Allura Red AC administered up to the maximum doses in mice., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Anthocyanins are increasingly valued in the food industry for their functional properties and as food colorants. The broadness of their applications has, however, been limited by the lack of stability of these natural pigment extracts in a number of food systems. The potential application of pyranoanthocyanins, anthocyanin derivatives with better stability conferred by the added pyran ring, as a food ingredient was determined. Methylpyranoanthocyanin (MPA) was prepared from reaction of acetone and anthocyanin extracts from red grapes. Reaction products were sequentially purified with polyamide resin, TSK gel resin and semi-preparative HPLC to a purity level >98%. Cytoprotective influence tests of the purified MPA indicated its significant protective effect against H2O2 induced MRC-5 cell damage. Results of evaluations of possible acute toxicity effects on MPA-fed mice, including macro and microscopic assessments, support the conclusion of a non-toxic effect of MPA, and its potential safe use as a food additive., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The thermodynamics of the interaction of the food colourant tartrazine with two homologous serum proteins, HSA and BSA, were investigated, employing microcalorimetric techniques. At T=298.15K the equilibrium constants for the tartrazine-BSA and HSA complexation process were evaluated to be (1.92 ± 0.05) × 10(5)M(-1) and (1.04 ± 0.05) × 10(5)M(-1), respectively. The binding was driven by a large negative standard molar enthalpic contribution. The binding was dominated essentially by non-polyelectrolytic forces which remained largely invariant at all salt concentrations. The polyelectrolytic contribution was weak at all salt concentrations and accounted for only 6-18% of the total standard molar Gibbs energy change in the salt concentration range 10-50mM. The negative standard molar heat capacity values, in conjunction with the enthalpy-entropy compensation phenomenon observed, established the involvement of dominant hydrophobic forces in the complexation process. Tartrazine enhanced the stability of both serum albumins against thermal denaturation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The E number system for food additives was introduced in the 1960s and the E was intended to reassure consumers that permitted additives were safe. In the 1980s full ingredient declarations had to be provided on food products for the first time and manufacturers were permitted to use either the name or the number of the additive on the ingredient list. This paper outlines some of the trends in the sourcing, use and labelling of additives since the introduction of full ingredient listing. Generally, sourcing has become more global with a large number of suppliers being based in China. From an initial use of E numbers in ingredient lists, manufacturers are increasingly using the names of additives. This trend is being extended to avoid the use of anything the consumer might consider an additive, particularly in connection with colours and preservatives. Specifically, the colours used in the Southampton study on the impact of food colours on hyperactivity in children have largely been replaced by colouring foodstuffs, and the preservative used in the study, sodium benzoate, has been replaced by potassium sorbate in the majority of soft drinks., (© 2014 Society of Chemical Industry.)

Soft drinks consumption is still a controversial issue for public health and public policy. Over the years, numerous studies have been conducted into the possible links between soft drink intake and medical problems, the results of which, however, remain highly contested. Nevertheless, as a result, increasing emphasis is being placed on the health properties of soft drinks, by both the industry and the consumers, for example, in the expanding area of functional drinks. Extensive legislation has been put in place to ensure that soft drinks manufacturers conform to established national and international standards. Consumers trust that the soft drinks they buy are safe and their quality is guaranteed. They also expect to be provided with information that can help them to make informed decisions about the purchase of products and that the information on product labels is not false or misleading. This paper provides a broad overview of available scientific knowledge and cites numerous studies on various aspects of soft drinks and their implications for health safety. Particular attention is given to ingredients, including artificial flavorings, colorings, and preservatives and to the lesser known risks of microbiological and chemical contamination during processing and storage.

Objective: Artificial food colourings and additives (AFCAs) have long been discussed to have adverse effects on cognition and behaviour in children. In this study, our aim was to assess the probable side effects of prenatal exposure to colouring food additives on neurobehaviour and spatial learning process., Methods: We administered 'no observable adverse effect levels' (NOAELs) of common used AFCAs as a mixture (erythrosine, Ponceau 4R, Allura Red AC, Sunset yellow FCF, tartrazine, Amaranth, Brilliant Blue, Azorubine and Indigotine) to female rats before and during gestation and tested their effects on spatial working memory and behaviour in their offspring. Effects of AFCAs on spatial working memory were evaluated by Morris water maze, behavioural and locomotor effects by open-field and forced-swim tests., Results: Prenatal exposure to commonly used AFCAs had no adverse effects on spatial working memory; however, assessment of interaction of sex and AFCAs on 'latency to locate the visible platform', which was used as a measure of motivation, showed a significant interaction (P < 0.05) on female rats. In addition, AFCAs caused an increase in anxiolytic like effect in the open-field test (P < 0.05) and an increase in mobility time (P < 0.05) in the forced-swim test. We also detected a significant interaction of sex and AFCAs on forced-swim test parameters (P < 0.05)., Discussion: These findings indicated that prenatal exposure to NOAELs of AFCAs resulted in implicit adverse effects that caused an increase in motility and a decrease in motivation and anxiety in offspring in sex-related manner.

This study reports an unusual case of IgE-mediated hypersensitivity to Cochineal red or Carmine red, a coloring agent of natural origin. Although the risk of anaphylactic reactions is well known, since the nineties the use of this additive seems to be nowadays on the rise. The problem of labeling of additives used in handmade food products is highlighted.

Background: Five recent reviews have analyzed trials on the association between artificial food colors and ADHD; the 50 underlying studies and the reviews in aggregate were inconclusive. Recent work has shown human in vivo SULT1A inhibition leading to incremental catecholamines, and an inverted-U relationship between brain catecholamines and proper functioning of the prefrontal cortex where ADHD behavior can arise., Method: This study re-examined the same underlying trials for evidence that SULT1A inhibitors were in the placebos and other inactive foods, that these "inactive" materials were symptomatic, and that ADHD symptoms exhibited an inverted-U response to SULT1A inhibition., Results: Nearly all the underlying diets, and many placebos and delivery vehicles, were found to contain SULT1A inhibitors. Eight publications provided evidence of ADHD symptoms caused by the "inactive" materials containing SULT1A inhibitors. Ten studies showed additional SULT1A inhibitors reducing the symptoms of some subjects., Conclusion: SULT1A inhibitors in foods, including natural substances and artificial food colors, have a role in ADHD that can both worsen or improve symptoms. Mechanistically, SULT1A enzymes normally deactivate catecholamines, especially dopamine formed in the intestines; SULT1A inhibition can influence brain catecholamines through the intermediary of plasma tyrosine levels, which are influenced by dopamine inhibition of intestinal tyrosine hydroxylase. Biochemical measurements focused on SULT1A activity and plasma tyrosine concentrations are proposed for future work., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Bulk- and nano-scale titanium dioxide (TiO2) has found use in human food products for controlling color, texture, and moisture. Once ingested, and because of their small size, nano-scale TiO2 can interact with a number of epithelia that line the human gastrointestinal tract. One such epithelium responsible for nutrient absorption is the small intestine, whose constituent cells contain microvilli to increase the total surface area of the gut. Using a combination of scanning and transmission electron microscopy it was found that food grade TiO2 (E171 food additive coded) included ∼25% of the TiO2 as nanoparticles (NPs; <100 nm), and disrupted the normal organization of the microvilli as a consequence of TiO2 sedimentation. It was found that TiO2 isolated from the candy coating of chewing gum and a commercially available TiO2 food grade additive samples were of the anatase crystal structure. Exposure to food grade TiO2 additives, containing nanoparticles, at the lowest concentration tested within this experimental paradigm to date at 350 ng/mL (i.e., 100 ng/cm(2) cell surface area) resulted in disruption of the brush border. Through the use of two independent techniques to remove the effects of gravity, and subsequent TiO2 sedimentation, it was found that disruption of the microvilli was independent of sedimentation. These data indicate that food grade TiO2 exposure resulted in the loss of microvilli from the Caco-2BBe1 cell system due to a biological response, and not simply a physical artifact of in vitro exposure.

The enzymatic oxidation of ferulic acid (FA) and ethyl ferulate (EF) with Myceliophthora thermophila laccase, as biocatalyst, was performed in aqueous medium using an eco-friendly procedure to synthesize new active molecules. First, the commercial laccase was ultrafiltrated allowing for the elimination of phenolic contaminants and increasing the specific activity by a factor of 2. Then, kinetic parameters of this laccase were determined for both substrates (FA, EF), indicating a higher substrate affinity for ethyl ferulate. Additionally, enzymatic oxidation led to the synthesis of a FA-major product, exhibiting a molecular mass of 386 g/mol and a EF-major product with a molecular mass of 442 g/mol. Structural analyses by mass spectrometry allowed the identification of dimeric derivatives. The optical properties of the oxidation products showed the increase of red and yellow colours, with FA-products compared to EF-products. Additionally, enzymatic oxidation led to a decrease of antioxidant and cytotoxic activities compared to initial substrates. Consequently, this enzymatic procedure in aqueous medium could provide new compounds presenting optical, antioxidant and cytotoxic interest., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Artificial food colors (AFCs) are widely used to color foods and beverages. The amount of AFCs the Food and Drug Administration has certified over the years has increased more than 5-fold since 1950 (12 mg/capita/day) to 2012 (68 mg/capita/day). In the past 38 years, there have been studies of adverse behavioral reactions such as hyperactivity in children to double-blind challenges with AFCs. Studies that used 50 mg or more of AFCs as the challenge showed a greater negative effect on more children than those which used less. The study reported here is the first to quantify the amounts of AFCs in foods (specifically in beverages) commonly consumed by children in the United States. Consumption data for all foods would be helpful in the design of more challenge studies. The data summarized here should help clinicians advise parents about AFCs and beverage consumption.

Food dyes serve to beguile consumers: they are often used to imitate the presence of healthful, colorful food produce such as fruits and vegetables. But considering the hurtful impact of these chemicals on the human body, it is time to thoroughly uncover the toxicity of these food dyes at the molecular level. In the present contribution, we have examined the molecular reactions of protein lysozyme with model food azo compound Color Index (C.I.) Acid Red 2 and its analogues C.I. Acid Orange 52, Solvent Yellow 2, and the core structure of azobenzene using a combination of biophysical methods at physiological conditions. Fluorescence, circular dichroism (CD), time-resolved fluorescence, UV-vis absorption as well as computer-aided molecular modeling were used to analyze food dye affinity, binding mode, energy transfer, and the effects of food dye complexation on lysozyme stability and conformation. Fluorescence emission spectra indicate complex formation at 10(-5) M dye concentration, and this corroborates time-resolved fluorescence results showing the diminution in the tryptophan (Trp) fluorescence mainly via a static type (KSV = 1.505 × 10(4) M(-1)) and Förster energy transfer. Structural analysis displayed the participation of several amino acid residues in food dye protein adducts, with hydrogen bonds, π-π and cation-π interactions, but the conformation of lysozyme was unchanged in the process, as derived from fluorescence emission, far-UV CD, and synchronous fluorescence spectra. The overall affinity of food dye is 10(4) M(-1) and there exists only one kind of binding domain in protein for food dye. These data are consistent with hydrophobic probe 8-anilino-1-naphthalenesulfonic acid (ANS) displacement, and molecular modeling manifesting the food dye binding patch was near to Trp-62 and Trp-63 residues of lysozyme. On the basis of the computational analyses, we determine that the type of substituent on the azobenzene structure has a powerful influence on the toxicity of food dyes. Results from this work testify that model protein, though an indirect method, provides a more comprehensive profile of the essence of toxicity evaluation of food dyes.

Objectives: To test the individual effect of artificial food colorings (AFCs) and a preservative on the behavior of the general Chinese population., Method: One hundred thirty children (70 boys and 60 girls) in Hong Kong with a mean age of 8.64 years were enlisted to the study with a within-subject crossover between AFCs, a preservative (sodium benzoate), and a placebo capsule. Two behavior scores were used including the strengths and weaknesses of attention deficit hyperactivity disorder and normal behavior rating scale and the child behavior checklist-teacher report form., Results: Capsule A containing AFCs and Capsule B containing sodium benzoate had no significant adverse effect compared with placebo in both behavior scores. This result persisted when analysis was restricted to children with 85% consumption of capsule (per protocol analysis)., Conclusion: There seem to be no significant associations between AFCs and a preservative on Chinese children's behavior at the age of 8 to 9 years. Future directions and implications of this research are discussed.

The safety of several azo colouring agents, used as food additives, has during the years been questioned. Allura Red AC (E129) has in some publications been classified as genotoxic. In fact, in the European Union, Allura Red is permitted as a food additive in human food, but, surprisingly, it was not acceptable as an additive for use in animal feed. In this study we have evaluated whether Allura Red is genotoxic using a flow cytometer-based micronucleus assay in peripheral blood of mice. Male FVB mice were given a single intra-peritoneal injection of various doses of Allura Red and sacrificed at 46 h after treatment. The tested doses were 0, 100, 200, 400, 600, 800, 1000, 1500, and 2000 mg/kg body weight (b.w.). Each dose group constituted three mice, except for in the dose group of 1000 mg/kg b. w., which constituted four mice. Blood samples were collected and the frequency of micronucleated polychromatic erythrocytes (fMNPCE) and the cell proliferation (%PCE) was determined. The analyses did not show any significant difference in the %PCE or in the fMNPCE. Consequently, under the testing circumstances one can conclude that Allura Red is not genotoxic., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Azo and diazo compounds include Sudan dyes, which were widely used in industry. Although they are not permitted in food, they had been found contaminating different food products and their presence is investigated regularly (since 2003) in these products. Sudan III, as well as Sudan Black B, was included in different laboratory techniques for tissue ceroid and lipofucsin analysis and blood-cell staining. Also, Sudan Black B has been recently included in in vivo evaluations in human beings (through oral intake), and Sudan III is still allowed in cosmetics. These azo dyes were metabolized to possible carcinogenic colorless amines, both in the liver of mammalians and by the micro flora present in human skin and the gastrointestinal tract. Both human and laboratory animal cytochrome P450s (CYPs) were able to oxidize Sudan I, whereas Sudan III modified CYP activities. In vitro genotoxic effects were reported for Sudan I, and some DNA adducts formed through exposure to its metabolites were identified. Sudan I was also found to be carcinogenic in the rat, but not in the mouse. The aim of the present review is to put together the most relevant information concerning Sudan dye uses and toxicity to provide some tools for the identification of the risk they represent for human health.