ArticleLiterature Review

Toxicology of food dyes

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Abstract

Background: Food dyes, synthesized originally from coal tar and now petroleum, have long been controversial because of safety concerns. Many dyes have been banned because of their adverse effects on laboratory animals or inadequate testing. Conclusions: This review finds that all of the nine currently US-approved dyes raise health concerns of varying degrees. Red 3 causes cancer in animals, and there is evidence that several other dyes also are carcinogenic. Three dyes (Red 40, Yellow 5, and Yellow 6) have been found to be contaminated with benzidine or other carcinogens. At least four dyes (Blue 1, Red 40, Yellow 5, and Yellow 6) cause hypersensitivity reactions. Numerous microbiological and rodent studies of Yellow 5 were positive for genotoxicity. Toxicity tests on two dyes (Citrus Red 2 and Orange B) also suggest safety concerns, but Citrus Red 2 is used at low levels and only on some Florida oranges and Orange B has not been used for several years. The inadequacy of much of the testing and the evidence for carcinogenicity, genotoxicity, and hypersensitivity, coupled with the fact that dyes do not improve the safety or nutritional quality of foods, indicates that all of the currently used dyes should be removed from the food supply and replaced, if at all, by safer colorings. It is recommended that regulatory authorities require better and independent toxicity testing, exercise greater caution regarding continued approval of these dyes, and in the future approve only well-tested, safe dyes.

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... In addition to the disruption of the activity of children, food dyes would be potentially implicated in other human health concerns. In individual works it was stated that for instance, dyes E102, E110, E129 and E133 would be the cause of hypersensitivity reactions [6,7]. On the other hand, dyes E127 and E102 would be reprotoxic. ...
... More specifically, these dyes would be the cause of a decrease in reproductive performance in male mice characterized by a reduction in the number of spermatozoa and an increase in abnormalities in these cells [8]. Much more serious, the dyes from petrochemical synthesis E102, E110 and E129 are contaminated with carcinogens [6,7]. Aside from dyes E110 and E129, dyes E123, E124 and E171 are at the origin of genotoxicity characterized by the induction of DNA damage [6,7,9,10]. ...
... Much more serious, the dyes from petrochemical synthesis E102, E110 and E129 are contaminated with carcinogens [6,7]. Aside from dyes E110 and E129, dyes E123, E124 and E171 are at the origin of genotoxicity characterized by the induction of DNA damage [6,7,9,10]. Also, the consumption of dyes E110, E129 and E171 or dyes E121, E127, E132 and E143 was found related to the triggering of different types of tumors [6,7,11]. ...
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Background Children are generally attracted to colorful foods. However, some food dyes are suspected of exacerbating the activity of children and inducing other health problems that can reach reprotoxicity and carcinogenicity. Objective This study aims to explore the presence of dyes such as E102, E104, E110, E121, E122, E123, E124, E127, E129, E132, E133, E143 and E171 in food products widely consumed by children in Algeria notably sweets and chocolates, beverages and ice creams, yogurts and biscuits. Material and Methods This work was carried out on 228 products including 57 biscuits, 47 drinks and ice creams, 20 yogurts and 104 sweets and chocolates. Information mentioned on the composition label of this products were recorded to determine the presence of studied dyes Results Here, we report the abundance of the yellow dyes E102 (24.1%) and E110 (18%) in the tested products. Also, apart from E121, all the other assessed dyes were found. Sweets and chocolates are the products containing the most studied dyes. The analysis of the presence of combinations of these dyes shows that 7% of analyzed foods contain 2 dyes in their composition while 20% of the products contain at least 3 dyes at the same time. Additionally, 37.5% of sweets and chocolates contain a combination of at least 3 dyes in their ingredient list. Conclusions In overall, except the E121, all assessed dyes were identified on the labels of food products widely consumed by children which encourage parents to be made aware of the risks associated with the ingestion of omnipresent dyes in children’s diets.
... Colorants are essential additives in food manufacturing, imparting vibrant colors to food and enhancing its sensory appeal. Synthetic colorants such as nitrite have been used to artificially color foods in industrialized nations for at least a century due to their greater cost-effectiveness, brighter colors, and better stability (Kobylewski & Jacobson, 2012). However, they have been unrevealed to pose considerable health risks to humans. ...
... However, they have been unrevealed to pose considerable health risks to humans. For instance, they might cause cancer, induce organ damage, trigger allergies, and potentially lead to attention-deficit hyperactivity disorder and affect neurodevelopment in children (Amchova et al., 2015;Kobylewski & Jacobson, 2012). Therefore, seeking natural alternatives to synthetic colorants has attracted increasingly attention. ...
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3‐Deoxyanthocyanidins, a rare class of anthocyanins, have gained increasing popularity due to their notable stability and bioactive properties. The enhanced stability of these colorants is attributed to the absence of a hydroxyl group at the C‐3 position. This absence leads to unique response mechanisms to environmental factors, such as pH, temperature, and light exposure. It also results in different interactions with biopolymers and co‐pigments. Sorghum is the only dietary source of 3‐deoxyanthocyanidins, which predominantly accumulate in the bran where the cell walls are extensively cross‐linked. This restricts their extraction, which is the premise of application. Therefore, this review compares the extraction efficiencies of 3‐deoxyanthocyanidins using conventional and innovative methods, discusses the qualification and quantification of such colorants, and summarizes factors affecting their stability, highlighting the differences in the behavior of anthocyanins and 3‐deoxyanthocyanidins influenced by these factors. This work provides insights for extracting and stabilizing 3‐deoxyanthocyanidins and proposes their potential applications in the food system.
... The Van Holten 'Pickle in A Bag' trend saw over 95 million views on the social media platform Tiktok, resulting in a surge of sales, and popular food vendors selling out (Louise, 2023). Although the pickle is labelled as healthy, fat-free and low in calories there is a presence of a carcinogenic food dye called 'yellow 5', and the pickle itself is additionally not fermented (Kobylewski & Jacobson, 2012). This trend highlights the demand for pickles, yet the current absence of authentic and fermented options on the market. ...
... A tendência "Pickle in a bag" de Van Holten teve mais de 95 milhões de visualizações na plataforma de mídia social Tiktok, o que resultou em um aumento nas vendas e no esgotamento de vendedores de alimentos populares (Louise, 2023). Embora o picles seja rotulado como saudável, sem gordura e com poucas calorias, há a presença de um corante alimentar cancerígeno chamado "amarelo 5", e o próprio picles também não é fermentado (Kobylewski & Jacobson, 2012). Essa tendência destaca a demanda por picles, mas a atual ausência de opções autênticas e fermentadas no mercado. ...
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Using communication design to create a brand identity, which is designed to educate young female adults on gut health and encourage healthier eating. Be Picky is a healthy snack option that advocates for good gut health, by educating and encouraging consumers to make healthier food choices, all while healing their gut. In recent years, studies have shown there to be an evident decline in human gut health, due to the decrease in probiotic-rich foods present in our diets. This leads to poor life quality and a series of other health implications. However, this can be prevented with an increased intake of good bacterias and probiotics, commonly found in fermented foods such as pickles. Using digital illustration, linocut and branding exploration through communication design to create a pickle brand made to benefit your gut health, tailored to appeal to the younger female audience. This project heavily relates to my own experiences regarding gut health, and how a solution like this would greatly improve the quality of life for so many, by motivating others to improve and maintain a healthy gut.
... Primary possible adulterants for tomato paste are cheap flours (starches) and artificial colours, the most dangerous being a cancer-causing dye, erythrosine [10]. Erythrosine, a poly-iodinated xanthene red dye ( Figure 1) used in food products, is reported to induce endotoxic and mutagenic effects in HepG2 cells [11], impairs thyroid function [12], and inhibits drug-metabolizing enzymes [13]. ...
... It is widely used in cosmetics, drugs, and food [12,14,36]. Although its utilization at low concentrations is permitted by the US FDA, cumulative evidence of toxicity pointing to studies suggesting it causes carcinogenicity, hyperactivity, and other neurobehavioral effects in children has resulted in calls by consumer groups to ban the colourant [10]. As a result of this, food regulatory bodies have made laws to control the use of this colourant. ...
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Tomato paste is the most consumed tomato product on the Ghanaian market, the majority of which are imported into the country. This food product is easily adulterated, and thus, routine quality checks are necessary. Therefore, the current study is aimed at assessing the quality of eight tomato paste products on the Ghanaian market and checking for the presence of starch and artificial colourant erythrosine as possible adulterants. Routine quality metrics such as the pH, titratable acidity, total solids, and total soluble solids were assessed using standard methods. An HPLC method was employed to detect the presence of the colourant erythrosine, whereas starch content was determined by an enzymatic method using α-amylase and then amyloglucosidase. Fifty percent of the products did not qualify to be called tomato paste based on total solid estimation. All the sampled products contained some amount of starch, with three having more than 10 g/100 g of this thickener. Additionally, the banned colourant erythrosine was detected in two of the products. All other parameters were consistent with regulatory standards. The present study has shown that some tomato paste products on the Ghanaian market contain additives that are not permitted under any circumstance and fall short of regulatory standards.
... Artificial food colors: Concerns have been raised concerning the potential carcinogenicity of artificial food coloring dyes including Red 40, Yellow 5, and Yellow 6, which have been discovered to be tainted with benzidine or other carcinogens (Kobylewski and Jacobson 2012). Citrus Red 2 is used sparingly on some Florida orange varieties, while Orange B has been phased out for a number of years, despite the fact that some dyes like these have raised safety concerns (Kobylewski and Jacobson 2012). ...
... Artificial food colors: Concerns have been raised concerning the potential carcinogenicity of artificial food coloring dyes including Red 40, Yellow 5, and Yellow 6, which have been discovered to be tainted with benzidine or other carcinogens (Kobylewski and Jacobson 2012). Citrus Red 2 is used sparingly on some Florida orange varieties, while Orange B has been phased out for a number of years, despite the fact that some dyes like these have raised safety concerns (Kobylewski and Jacobson 2012). ...
Chapter
Considering a steady increase in the consumption of juices, the production and processing of the same have been dramatically increased in the past decades. Such upward movement in the graph resulted from various factors. The nutritional goals of an average healthy human require a balanced mixture of micro and macronutrients. Fruits and some vegetables in the form of juice are a more convenient way of consumption, providing relaxation to the digestive mechanism from the digestion of fibers. The chapter covers various aspects of processed juices as the glycemic response associated with juice intake and its significance for individuals particularly those with metabolic concerns, and enamel erosion due to juice consumption with a focus on the acidity levels inherent in different juices and strategies to mitigate their effects on dental health. In addition to this, the toxicity considering the natural toxicants and additives commonly found in commercial juices, the presence of heavy metals (HMs) and their associated toxicities, and the potential risks posed by microbial contaminants have been discussed critically. Packaging techniques employed in juice preservation are evaluated, emphasizing their benefits in maintaining quality and extending shelf life.
... In Europe, the European Food Safety Authority (EFSA) and, in the United States, the Food and Drug Administration (FDA) have limited the use of synthetically sourced colorants in foods, beverages, and confectionery. These decisions come after suspicion or confirmation of allergic reactions and carcinogenic effects associated with using these food colorants (Kobylewski and Jacobson, 2012). This has resulted in a shift to natural colorants for applications in food industries, specifically the confectionary and beverage industries. ...
Article
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The objective of this study was to examine the influence of chocolate formulation (sweetener and color) on consumer sensory acceptance and emotional response across two consumer populations, Brazilian and Polish. White chocolate samples (n = 10) were formulated with differences in sweetener (sucrose, rebaudioside A) and color (red, blue, yellow, green). Along with a trained panel, consumers in Brazil (n = 120) and Poland (n = 120) evaluated chocolate samples for liking and associated emotions. Color was not found to influence sweetness or flavor perception, indicating the absence of cross‐modal influence. However, the yellow‐colored chocolate was liked less than the blue, green, or red chocolate. Emotions were a stronger driver of product liking in the Brazilian population compared to the Polish consumers. This research shows the influence of color on consumers perception, with implications of using natural colors in chocolate production and “yellowing” in white chocolate. Practical Applications The recipe may be used in chocolate manufacturing to produce free‐sugar chocolate targeted to consumers with health conditions, such as diabetes. Our research also gives the solution for practical application of natural dyes to white chocolate to cover the problematic “yellowing,” which is considered defect of this product and results in the low consumer acceptance. The dyes that are suggested to add are of red, green, or blue color due to high acceptability of consumers from different countries.
... In the manufacturing of isotonic beverages, flavorings and synthetic dyes that possess sensory attributes resembling those of fruits are employed. Nevertheless, empirical investigations have identified consumer concerns over the chemical composition of those beverages (Porfírio et al., 2019;Kobylewski & Jacobson, 2012). ...
Article
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This study explores the formulation and evaluation of a novel isotonic sports drink using dates of Ajwa variety (Phoenix dactylifera L.) as a natural alternative to synthetic ingredients commonly found in commercially available sports beverages. Ajwa dates were selected for their rich bioactive components, including natural sugars, phenolic compounds, and essential minerals, which align with the functional requirements of isotonic drinks. Three formulations (ASD1, ASD2, ASD3) were developed by varying the ratio of Ajwa date pulp to deionized water, and these formulations were evaluated for their physicochemical properties, mineral content, antioxidant capacity, microbiological safety, and sensory acceptance. The ASD2 (25 % pulp) emerged as the most promising, with the highest sensory scores (8.2/9 in overall acceptability). ASD2 demonstrated excellent phys-icochemical stability over a 90-day storage period, maintaining an osmolality of 297 ± 3.17 mOsm/kg, suitable for rapid hydration. The formulation achieved an optimal pH of 4.62 ± 0.12 and provided 34.01 ± 0.47 kcal/ 100 g energy, sufficient for replenishing energy during physical activity. Microbiological tests confirmed the safety, with minimal total plate count (1 cfu/mL) and no detected coliforms or molds. Notably, the drink retained its antioxidant capacity, with ascorbic acid levels around 1 mg/100 mL and phenolic content ranging between 2.5 and 3.0 g/kg gallic acid equivalent. The study concludes that the Ajwa date isotonic sports drink is a promising natural alternative for athletes, offering both hydration and additional health benefits. This research highlights the potential for using natural ingredients in sports nutrition and provides a foundation for future studies on the commercialization of such products.
... In the manufacturing of isotonic beverages, flavorings and synthetic dyes that possess sensory attributes resembling those of fruits are employed. Nevertheless, empirical investigations have identified consumer concerns over the chemical composition of those beverages (Porfírio et al., 2019;Kobylewski & Jacobson, 2012). ...
Article
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1 Highlights • Developed an isotonic sports drink with Ajwa dates as a natural alternative. • Assessed the physicochemical and microbiological properties of three formulations. • The ASD2 formulation (25% Ajwa pulp) showed best sensory qualities. • ASD2 (25% Ajwa pulp) had the best sensory attributes and stayed stable for 90-days. • The study highlighted the Ajwa dates' potential in sports nutrition. Abstract: This study explores the formulation and evaluation of a novel isotonic sports drink using dates of Ajwa variety (Phoenix dactylifera L.) as a natural alternative to synthetic ingredients commonly found in commercially available sports beverages. Ajwa dates were selected for their rich bioactive components, including natural sugars, phenolic compounds, and essential minerals, which align with the functional requirements of isotonic drinks. Three formulations (ASD1, ASD2, ASD3) were developed by varying the ratio of Ajwa date pulp to deionized water, and these formulations were evaluated for their physicochemical properties, mineral content, antioxidant capacity, microbiological safety, and sensory acceptance. The ASD2 (25% pulp) emerged as the most promising, with the highest sensory scores (8.2/9 in overall acceptability). ASD2 demonstrated excellent physicochemical stability over a 90-day storage period, maintaining an osmolality of 297±3.17 mOsm/kg, suitable for rapid hydration. The formulation achieved an optimal pH of 4.62±0.12 and provided 34.01±0.47 kcal/100 g energy, sufficient for replenishing energy during physical activity. Microbiological tests confirmed the safety, with minimal total plate count (1 cfu/mL) and no detected coliforms or molds. Notably, the drink retained its antioxidant capacity, with ascorbic acid levels around 1 mg/100 mL and phenolic content ranging between 2.5-3.0 g/kg gallic acid equivalent. The study concludes that the Ajwa date isotonic sports drink is a promising natural alternative for athletes, offering both hydration and additional health benefits. This research highlights the potential for using natural ingredients in sports nutrition and provides a foundation for future studies on the commercialization of such products.
... B1 can inhibit nerve cell development, and it has been related to skin irritations and bronchial constriction [40,41]. B2 has been shown to increase brain gliomas and malignant mammary gland tumors in a rat model [42,43]. According to these results, tar colors stimulate the production and release of inflammatory biomarkers [25]. ...
Article
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Sixteen color additives (tar colors) were detected in 128 food samples (macarons, meringue cookies, and coque macarons) using HPLC with a photodiode array detector at 420 nm, 520 nm, and 620 nm for the yellow, red, and blue and green color types, respectively. The tar color recovery rates ranged from 81.3 to 95.6%, and their limits of detection (LOD) and quantification (LOQ) were 0.001–0.049 mg/kg and 0.004–0.147 mg/kg, respectively. Seven tar colors (Y4, Y5, R3, R40, R102, B1, and B2) were detected in 129 samples. All the samples did not contain nine tar colors (R2, G3, Azo, R106, QY, ORII, BBN, PBV, and GS). The quantity of tar colors (Y4, Y5, R40, and B1) in 15 samples exceeded the Korean Ministry of Food and Drug Safety (MFDS) standard. Ninety samples (70%) used a mixture of two or more tar colors, and the amount used was 11.0–1643.3 mg/kg. The quantity of combined tar colors in 15 samples exceeded 300 mg/kg. Through these findings, this study aims to contribute to the development of safer and more reliable desserts containing tar colors, by enhancing safety measures and ensuring improved quality control for consumer protection.
... However, it is important to note that the application of these colors can potentially result in adverse health effects, including toxicity and even carcinogenicity in humans (Durazzo et al., 2022). The empirical evidence gathered by researchers suggests that the utilization of synthetic pigments is associated with detrimental consequences, including the manifestation of allergies such as asthma and urticarial, an elevated likelihood of developing cancer, impairment to the liver, and kidneys, an increased probability of experiencing miscarriage, diminished cognitive focus, and intelligence quotient in young individuals, the occurrence and exacerbation of issues in children with hyperactivity, a decline in the efficacy of the immune system, and disturbances in sleep patterns (Kleinman et al., 2011;Kobylewski and Jacobson, 2012). Studies have discovered a notable correlation between the ingestion of synthetic pigments in a range of food items and the magnitude of the ailment in children afflicted with hyperactivity (Farzianpour et al., 2013;Yamjala et al., 2016). ...
Article
Background: The use of additives, especially food colors, has attracted the attention of food industries. The purpose of this study is to retrospectively investigate the use of food colors in food products offered in Urmia, Iran. Methods: In this study, 451 samples of different types of food were collected from Urmia (April 2019-February 2022). To identify the color type, the Thin Layer Chromatography method was used. The samples included a confections (dry sweets), saffron noghl, saffron halva (a type of confectionery originating from Persia and widely spread throughout the Middle East), saffron-flavored rice and chicken, fruit ice cream, traditional saffron-flavored ice cream, fruit drinks, and saffron solutions. These products were produced from establishments engaged in the production and distribution of food and confections, restaurants, halva manufacturing workshops, traditional ice cream production workshops, and coffeehouses. Statistical analysis of data was done using SPSS software (IBM SPSS statistic 16, USA). Results: Within the group of synthetic dyes analyzed, quinoline yellow, sunset yellow, carmoisine, and tartarazine were identified as the most commonly used synthetic colorants in the examined food products. Findings also showed that rice and saffron chicken samples had the highest average frequency of tartarazine used among the studied food groups (41.66±1.88%). The highest mean frequency of yellow quinoline consumption was also observed in samples of saffron halva (57.27±3.86%), various types of dry sweets (55.50±0.7%), and saffron noghl (52.50±3.53%). Sunset yellow had a low frequency in all groups except saffron ice cream and fruit drinks (p=0.086). The findings showed that the highest average frequency of carmoisine synthetic color consumption was related to saffron ice cream (25±1.41%) and fruit drinks (23.80±2.54%) among the studied food groups. Conclusion: The findings indicated that approximately 30% of the tested samples, except fruit drinks, contained synthetic colorants.
... While the systemic toxicity of nicoracine dye specifically is not well-documented, certain azo dyes have been associated with adverse health effects when ingested or absorbed into the body [14]. Ingestion of food products containing nicoracine dye as a color additive may raise concerns about potential systemic toxicity, although regulatory authorities generally establish safety thresholds to minimize health risks [15]. Some azo dyes, including certain members of the azo dye class to which nicoracine belongs, have been found to possess genotoxic and carcinogenic properties in laboratory studies [16]. ...
Article
This study explores the green synthesis of lead nanoparticles and their application in degrading the AZO dye Nicoracine under solar irradiation. UV-Visible spectroscopy confirmed nanoparticle formation with a peak at 248 nm, indicating SPR. FTIR revealed functional groups from plant extracts aiding stabilization. XRD analysis showed a crystalline structure, while SEM and AFM indicated irregular shape and rough surface. The nanoparticles exhibited significant catalytic activity, enhancing Nicoracine degradation via solar light, facilitated by ROS generation. Kinetic analysis suggested a pseudo-first-order reaction model. This green synthesis method offers a sustainable solution for wastewater treatment and industrial pollution mitigation.
... However, food regulations in many countries permit its use within specific limits, making it one of the most commonly used dyes in food products. Tartrazine can be found in various items, such as soft drinks, sports drinks, flavored potato products, sauces and jellies, and in non-food products, including soaps, cosmetics, vitamins and medications [20][21][22]. Finally, the analysis of the samples was carried out using HPLC and the results were compared using statistical tests. ...
Article
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Analytical instrumentation is essential for chemical analysis in many fields, including biology and chemistry, but it can be costly and inaccessible to many educational institutions because it often requires expensive and sophisticated equipment. To address this issue, there has been growing interest in developing new and accessible alternatives. In this study, we developed a low-cost and user-friendly spectrophotometric detector based on an Arduino UNO platform. This detector was coupled with a flow injection analysis system (FIA) and used to quantify the concentration of tartrazine in commercial beverages and candy samples. The proposed miniaturized detector offers an affordable and portable alternative to conventional spectrophotometers. We evaluated the performance of our detector by comparing its results with those obtained using high-performance liquid chromatography (HPLC-DAD), and the accuracy and precision were comparable. The results demonstrate the potential of the Arduino-based spectrophotometric detector as a cost-effective and accessible tool, with potential applications in food science, environmental monitoring, and other fields.
... Specifically, food and textile industries are using enormous amounts of various synthetic organic dyes, which play a key role in environmental pollution [5]. Because synthetic organic dyes are non-biodegradable and show toxicity and carcinogenic effects on living organisms [6,7]. In particular, MB, a thiazine cationic dye could cause ...
Article
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The current study examines the synergistic effect of manganese oxide (MnO2)/graphitic-carbon nitride (g-C3N4) nanocomposite for degradation (decolorization) of methylene blue (MB) and acid blue 113 (AB113) in an aqueous solution. XRD, HR-SEM, HR-TEM, and EDX analysis confirmed the successful loading of g-C3N4 nanoparticles (NPs) on the. MnO2 NPs. FTIR confirms the functional groups and presence of interaction between MnO2 and g-C3N4 NPs. UV–Visible spectra predict an improvement in light absorption ability of MnO2 NPs after loading of g-C3N4. Photoluminescence (PL) spectral analysis indicates the effective charge separation ability of MnO2/g-C3N4 nanocomposite. HR-SEM and HR-TEM analysis portray the formation of hexagonal-like MnO2 particles and g-C3N4 nanosheets. The photocatalytic degradation of MB and AB113 dyes in presence of pure MnO2 and MnO2/g-C3N4 nanocomposite was studied under visible light irradiation. The maximum degradation efficiency was found to be 97% for MB and 92% for AB113 dye, in the presence of MnO2/g-C3N4 nanocomposite. The scavenger studies were performed to examine the responsible active species for the degradation of dyes. The prepared MnO2/g-C3N4 nanocomposite also showed acceptable recyclability in the dye photodegradation reactions.
... The dyes used in food colourants are mostly synthetic and are organic complex compounds that are produced from coal tar and petroleum. The choice of dyes used by the industries stuck to the synthetic because they are cheaper, stable, and brighter than the natural ones [74]. ...
Chapter
Dyes, being natural or synthetic, are renowned for their vibrant colours, which come from a group of atoms known as chromophores. There are around 14 different types of dye. The majority of dyes are used by textile industries for fabric manufacturing, and many of these dyes are toxic in nature and possess complex structures. During dyeing and finishing operations, nearly 2 lakh tonnes of dye are introduced into water bodies. Due to their exceptional stability against heat, temperature, light, chemicals, water, and other parameters, these dyes are sustained in the environment for a long period of time, causing severe harm to marine and aquatic bodies. In order to have minimal effects of dyes on the environment, we must look for alternatives or find out effective methods to degrade these hazardous chemicals. This chapter aims to delve into the creation of dyes, their widespread usage, the detrimental effects on our environment, and the techniques available to identify dye pollution.
... Many colorants developed by humans have relied on heavy metals and are highly toxic both to human health and to the environment, 1 such as the use of arsenic to produce green fabrics and wallpapers. 2,3 Even today, many paints, colorants, and dyes are toxic to human health and/or the environment, leading to a continual need for sustainable, environmentally friendly, and non-toxic options. 4 The ability to produce color from new materials-especially non-toxic and biodegradable materialspromises to revolutionize colorants. ...
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This Tutorial introduces structural color in fruits as a phenomenon of diverse optical materials. Originally best known in abiotic materials and animals, structural colors are being increasingly described in plants. Structural colors have already inspired a variety of useful products, and plants are especially attractive as models to develop new bioinspired technologies thanks to the comparative ease of working with them compared with animal systems. Already, human-engineered structural colors modeled after plant cellulose-based architectures have shown promising applications in colorants and sensors. However, structural colors include a far broader group of materials and architectures beyond cellulose. Understanding the new and diverse structures that have recently been described in plants should provoke research into new bioinspired products based on plant optical structures and biomaterials. In this Tutorial, we focus on fruits as new structures have recently been discovered, leading to new opportunities for bioinspired technologies. We bring together a review of optical structures found in fruits from a physical optics perspective, with a consideration of each structure as an opportunity in bioinspired and biomimetic design.
... A significant and novel aspect of our findings is that a synthetic blue colorant, brilliant blue FCF, can modulate hemostasis; the experiments were carried out on human whole blood, plasma, and blood platelets in vitro. The effect of brilliant blue on metabolism, as well as its neurotoxicity, genotoxicity, and carcinogenicity, were studied in various experiments [43,[47][48][49][50]. However, there is only one paper demonstrating its effect on hemostasis [51]. ...
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Natural and synthetic colorants present in food can modulate hemostasis, which includes the coagulation process and blood platelet activation. Some colorants have cardioprotective activity as well. However, the effect of genipin (a natural blue colorant) and synthetic blue colorants (including patent blue V and brilliant blue FCF) on hemostasis is not clear. In this study, we aimed to investigate the effects of three blue colorants—genipin, patent blue V, and brilliant blue FCF—on selected parameters of hemostasis in vitro. The anti- or pro-coagulant potential was assessed in human plasma by measuring the following coagulation times: thrombin time (TT), prothrombin time (PT), and activated partial thromboplastin time (APTT). Moreover, we used the Total Thrombus formation Analysis System (T-TAS, PL-chip) to evaluate the anti-platelet potential of the colorants in whole blood. We also measured their effect on the adhesion of washed blood platelets to fibrinogen and collagen. Lastly, the cytotoxicity of the colorants against blood platelets was assessed based on the activity of extracellular lactate dehydrogenase (LDH). We observed that genipin (at all concentrations (1–200 µM)) did not have a significant effect on the coagulation times (PT, APTT, and TT). However, genipin at the highest concentration (200 µM) and patent blue V at the concentrations of 1 and 10 µM significantly prolonged the time of occlusion measured using the T-TAS, which demonstrated their anti-platelet activity. We also observed that genipin decreased the adhesion of platelets to fibrinogen and collagen. Only patent blue V and brilliant blue FCF significantly shortened the APTT (at the concentration of 10 µM) and TT (at concentrations of 1 and 10 µM), demonstrating pro-coagulant activity. These synthetic blue colorants also modulated the process of human blood platelet adhesion, stimulating the adhesion to fibrinogen and inhibiting the adhesion to collagen. The results demonstrate that genipin is not toxic. In addition, because of its ability to reduce blood platelet activation, genipin holds promise as a novel and valuable agent that improves the health of the cardiovascular system and reduces the risk of cardiovascular diseases. However, the mechanism of its anti-platelet activity remains unclear and requires further studies. Its in vivo activity and interaction with various anti-coagulant and anti-thrombotic drugs, including aspirin and its derivatives, should be examined as well.
... Red and violet color characteristics are the result of various substitution patterns in betacyanins, while different amino acid or amine side chains determine the color of betaxanthins [15,16]. Comparative assessment for utilization of microbial pigments as food colorants was affirmed by metabolic engineering and nanotechnology in yielding safety and security of food colorants than natural additives [2,7,17,18]. Similarly, extensive reviews by several researchers throughout the world emphasized the application of microbial pigments in nutraceuticals [19], biotechnological potentials [20,21], and bioactive potentials in abating the majority of diseases [6]. ...
Article
Pigments are widely used in food supplements envisaging attractive colors along with health benefits. The desired advancements in the nutraceutical and antioxidant properties of pigments utilized in food products necessitate the search for novel additives. The present study is the first in the field to report the pigment-producing endolichenic bacteria, Bacillus sp. LDAB-1 from Dirinaria aegilita. Morphological, biochemical, and molecular characterization of the bacterium emphasizes that ideal pigment production occurs when utilizing sucrose and sodium nitrate. The pigment was salted out and dialyzed for further qualitative characterization using ultraviolet–visible, fluorescence, and Fourier transform infrared spectra and the results corroborated the presence of betalains. The antioxidant activity of betalain is closer to the efficiency of α-tocopherol, which confers the pigment properties for antioxidant and nutraceutical significance. An optimal methodology for pigment affirmation is an issue when using an alternative methodology. Hence, the present assessment employs a comparative analysis of findings from both a spectrophotometric method and image processing technology encompassing RGB, CMYK, YCbCr, and L*a*b* color space models. Amongst these, the L*a*b* model potentially provides an effective modality for determining the pigment concentration. Bland–Altman plot analysis indicates similar consistency levels in betalain quantification by both methods at 95% confidence intervals, affirming the integrity and consistency of color image processing technology. Consequently, the present study represents novelty and innovativeness in reporting endolichenic Bacillus sp. LDAB-1 from D. aegilita and a rational image optimization protocol for pigment elucidation characteristics.
... It appears that those microbes metabolize the food dyes to create ANSA-Na, which induces a relapse of the colitis [147]. In conclusion, food colorants/dyes can be regarded as adjuvants since they can be immunostimulant for human lymphocytes, activate cell-mediated immune responses and increase immunoglobulin's secretion, and induce cross-reactive antibodies [132,[148][149][150]. Finally, some experts suggested that "the evidence for carcinogenicity, genotoxicity, and hypersensitivity, coupled with the fact that dyes do not improve the safety or nutritional quality of foods, indicates that all of the currently used dyes should be removed from the food supply and replaced, if at all, by safer colorings" [151]. Or, "we strongly believe that the use of these potentially toxic colors in food needs to be reconsidered" [152]. ...
... For example, 'azo dye' shows resistance to microbial degradation in wastewater treatment systems (Hussein and Scholz 2018). Artificial food colouring can create human hazards due to cancer-causing toxic materials, animal threats, and increasing hypersensitivity, especially among children (Kobylewski and Jacobson 2012;Okafor et al. 2016). ...
Article
A light pink-coloured, rod-shaped, gram-negative bacterium isolated from an unproductive crude oil production area was considered as a sample for this study. The 16S rRNA gene sequence identified the isolate as Methylobacterium komagatae. Comparing the standard colour measurement values set by the International Commission on Illumination (CIE) method confirms the colourant produced by the biomass of this microorganism as a 'light pink' colouration. The energy-dispersive X-ray spectroscopy and High-Resolution Mass Spectroscopy process help in the structural elucidation of the sample. It indicates the presence of magnesium (Mg) as a central metal atom in the bacterial colourant, i.e. 'bacteriochlorophyll' (BChl) (MgC55H74N4O). The recovered bacterial colourant was applied to cotton fabric and cotton yarns to dye and examine their fastness quality. The result shows the cotton fabrics retained colourant in normal washing while it got reduced after detergent-based washing. Therefore, its fastness quality must be improved to equalise with current colourants.
... Epidemiological studies suggested that most synthetic dyes are highly toxic in nature which leads to cancer; moreover, these dyes are a serious threat to nature too (Kobylewski & Jacobson, 2012). Therefore, recent studies encourage the replacement of these toxic dyes with non-toxic natural extracts from different parts of the plant (Roy & Rhim, 2022). ...
... One of the important advantages of synthetic food colorants is that it is cheap, easily available, and more stable than natural food colorants. Despite possessing plenty of advantages, synthetic food colorants can cause an ample of diseases and disorders including hypersensitivity reactions (caused by blue, red, and yellow dyes), carcinogenic effects (red and yellow dyes), and genotoxicity (red and orange dyes) (Kobylewski & Jacobson, 2012). Therefore, the shift to natural food colorants is occurring, these colorants not only impart color but also fortify the food by adding their physicochemical and bioactive functionalities. ...
Article
Phycocyanin is a blue accessory protein pigment that is abundant in Spirulina sp. and has gained popularity due to its diverse applications in various industries. Phycocyanin is rich in natural properties that can be used as a nutraceutical, combining food and pharmaceutical sectors. It has been explored in the pharmaceutical industry by combining with disease-specific drugs and has been experimented against various conditions such as cancer, anemia, inflammation, diabetes, obesity, and neurodegenerative disorders. Additionally, phycocyanin has been used as a natural alternative to artificial food colorants, which imparts color to food and boosts the nutrient value of the food. The market value of phycocyanin is projected to reach $279.6 million by 2030, with a CAGR of 28.1%. Despite its various benefits, phycocyanin has some drawbacks, including instability towards light, pH, and temperature, lower yield, and higher production costs, which limit the expansion of the industry. This comprehensive review provides an overview of different aspects of phycocyanin production and utilization, including Spirulina cultivation, various extraction and purification strategies, and its applications predominantly in food industries and other allied sectors.
... Six artificial food dyes including sunset yellow, allura red, ponceau 4R, tartrazine, carmoisine and quinoline yellow have been attributed to a spike in children's hyperactivity [2]. The inclusion of synthetic colours is harmful because of the existence of cancer-causing elements which induce allergic reactions [3]. Consumers prefer to use natural colourants rather than synthetic ones since natural colours are healthier and impart food characteristics such as flavour and appearance. ...
Article
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Annatto, a natural food colourant, varies from red to orange shades extracted from the seeds of the tropical plant achiote tree (Bixa orellana L.). The important carotenoids found in annatto seeds are bixin and norbixin, which are widely employed as colouring agents in processed food products such as butter, cheese, biscuit cream, paneer, salami, sugar cones, wafers, sausages, fish, margarine, and confectionery. An effective mechanical extraction unit was developed with a capacity of 3 kg for the extraction of pigments from the annatto seeds outer coat, based on the impact of leaching. The current study investigates the effect of water as a solvent by optimizing the process variables such as pressure (1, 3, and 5 bar), time (5, 10, and 15 min), temperature (30, 40, and 50°C), and annatto seed: water ratio (solvent) of 1:1 and 1:2 in mechanical extraction unit using Central Composite design. The optimized condition of pressure, temperature, residence time, and the seed-solvent ratio was 5 bar, 40°C, 10 min, and 1:1 conditions were statistically significant (p<0.05) yielding a maximum of 3.41 % bixin, 1.41 % norbixin, and 44.43° hue angle. The error percentage was less than 2 % indicating the model’s accuracy. Thus, the developed mechanical extraction unit was found to be the best method to leach out maximum pigment from the annatto seeds that can be used as a natural food colourant.
... Therefore, the use of various additives including synthetic food dyes raises concerns about food safety. Food dyes cause allergic reactions, mutagenic, carcinogenic, genotoxic, and cytotoxic effects depending on the dose, duration, and type [9][10][11]. It has also been reported that chronically consumed food additives cause cognitive and locomotive dysfunctions in the brain and alter the microbiota through the brain-gut axis [12]. ...
Article
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Background Azo dyes are widely used in the food industry to prevent color loss during processing and storage of products. This study aimed to investigate the effect of a diazo dye Brilliant Black PN (E151) on oxidative stress-related parameters in fruit flies (Drosophila melanogaster) at biochemical and molecular levels. Methods and results Third instar larvae were transferred to a medium containing the dye at different doses (1, 2.5, and 5 mg/mL). Gene expression and activity of superoxide dismutase, catalase (CAT), glutathione peroxidase (GPX), and acetylcholinesterase (AChE) enzymes were determined in the heads of adult flies obtained from these larvae. In addition, the glutathione (GSH) and malondialdehyde levels were measured using spectrophotometric analysis. Mitochondrial DNA (mtDNA) copy number was also detected by real-time PCR. The results showed that treatment with 5 mg/mL of the dye caused a decrease in both gene expression and enzyme activity of CAT and GPx. Moreover, the same dose of dye treatment decreased AChE activity, GSH level, and mtDNA copy number. Conclusions As a result, Brilliant Black PN dye can trigger toxicity by altering the level and activity of oxidative stress-related biomarkers in a dose-dependent manner. Therefore, more comprehensive studies are needed to elucidate the side effect mechanism and toxicity of this dye.
... Several dyes have already been associated with an increase in the effects of attention deficit hyperactivity disorder. Other health problems have been associated with the ingestion of artificial dyes, such as allergies, thyroid tumors, hives and respiratory problems [2]. Thus, in recent decades, various food colorings have been banned and those allowed are strictly controlled by laws, regulations and values of acceptable daily intake. ...
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Calibration is a fundamental step in instrumental quantitative methods that produce an analytical signal proportional to the concentration of the analyte in the sample. Multi-wavelength calibration (MWC), a novel calibration strategy, has been proposed as a simple method for the determination of analytes in samples with complex matrices. It has minimal matrix effects and straightforward sample preparation. The objective of this work was to apply this calibration strategy to the determination of the synthetic dye Sunset Yellow in soft drinks by high-performance liquid chromatography with ultraviolet–visible analysis (HPLC/UV–Vis). Multi-wavelength calibration planning was performed as recommended in the literature. MWC results were statistically compared with conventional external calibration (limit of detection, limit of quantification, linearity, repeatability and recovery). The results obtained with both calibrations showed that the soft drinks complied with Brazilian legislation. The dye contents obtained with both calibration methods did not show significant statistical differences. MWC appears as an alternative or complement to external calibrations and ensures minimal matrix effects and straightforward sample preparation.
Article
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.
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We have been indoctrinated into believing truths founded in tainted research and flawed opinions. These lies have, impart, caused America's obesity rate to surpass 40% of adults. While eating healthy is a part of a healthy lifestyle and beneficial for physical health, it is not the full scope of the awareness we should be equipped with. Items we eat out of, touch, wear, and breathe all contribute to a hormonal epidemic. In men, testosterone is rapidly decreasing causing all kinds of reproductive, physical, and mental issues. Testosterone being the building block of a man, it is no wonder modern men are suffering an abundance of issues that were previously unheard of. Synthetic materials bringing strength, durability, and elasticity were intended for the benefit of society, but it seems they have been the downfall. Instead of properly researching this new magic material it has been coined as the new steel, and more than that. These plastics are being used in our packaging for both food and drink, as well as being used as the core for clothes, hygiene products, shoes, and glasses; practically everything we use has some sort of plastic element within it.
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The design and fabrication of smart and low-cost nanocomposites (NCs) is still an area of challenge in wastewater treatment. In this context, firstly individual graphene oxide (GO) and cerium oxide (CeO2) nanoparticles (NPs) were synthesized by precipitation method. This was followed by synthesis of GO-CeO2-NCs by mixing GO and CeO2-NPs in natural surfactant which was characterized by UV–visible absorption spectroscopy. The morphology of the synthesized GO-CeO2-NCs was established by scanning electron microscopy (SEM) studies while high resolution transmission electron microscopy (HRTEM) analysis revealed shape and particle size of the synthe sized NCs. Fourier transform infrared spectroscopy (FTIR) was used to confirm the presence of different func tional groups in the synthesized GO-CeO2-NCs and thermal stability was determined by thermal gravimetric analysis (TGA). The synthesized GO-CeO2-NCs was used as catalyst in heterogeneous Fenton process for the degradation of methyl violet (MV) dye. The effects of various experimental parameters, i.e., pH, H2O2, GO-CeO2 NCs for MV degradation were investigated to have optimum condition. The optimum conditions for effective degradation with 98 % was achieved just within 100 minutes, at pH=8, [H2O2] 80×10 4 M, and [GO-CeO2] 18 mg/L for 3×10 3 M degradation. The experimental observations have led up to propose a most plausible mechanism for GO-CeO2-NCs enhanced Fenton’s degradation of MV. GO-CeO2 nanocomposites with H2O2 shows amazing removal capacities in the elimination of MV. In summary, synthesized GO-CeO2 nanocomposites demonstrate remarkable efficiency in present work, and offering a promising solution for the effective degra dation of methyl violet dye in wastewater treatment.
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The presented review concerns the cross-disciplinary approaches to the subject of blue food and blue colourants, the socio-cultural aspects of blue food and beverage consumption, human health effects, environmental impact, and economic aspects. Blue colour in relation to food is not only about improving visual appeal, to which the addition of food colouring is usually limited when the food is coloured in some way that does not encourage eating. It is also the rich and complex sociological side related to food, that is, not only the food itself but also the background, dishware, and light, depending on whether we want to encourage—to increase consumption—or discourage—to, for example, reduce the amount of food eaten for dietary purposes. The negative side of consuming and disposing of synthetic dyes and the health-promoting aspects of natural dyes are also mentioned, with the economic and environmental aspects of sourcing natural dyes being discussed. The food industry uses blue dyes not only for consumption, but also for food quality control, taking advantage of the pH-dependent colour change properties of the compound.
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Exploring extremotolerant and extremophilic microalgae opens new frontiers in sustainable biotechnological applications. These microorganisms thrive in extreme environments and exhibit specialized metabolic pathways, making them valuable for various industries. The study focuses on the ecological adaptation and biotechnological potential of these microalgae, highlighting their ability to produce bioactive compounds under stress conditions. The literature reveals that extremophilic microalgae can significantly enhance biomass production, reduce contamination risks in large-scale systems, and produce valuable biomolecules such as carotenoids, lipids, and proteins. These insights suggest that extremophilic microalgae have promising applications in food, pharmaceutical, cosmetic, and biofuel industries, offering sustainable and efficient alternatives to traditional resources. The review concludes that further exploration and utilization of these unique microorganisms can lead to innovative and environmentally friendly solutions in biotechnology.
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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 (EOCRC) 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 towards 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.
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The book Medicinal Plants and Healing of Human Health Focuses on differentaspect of the importance of medicinal plants and human health. Every civilization has employed herbal medicine to cure and prevent illness throughout history. The resources used in each culture were those that were accessible in the area and cateredto regional health issues. Cultural traditions were exposed through immigration and trade, where they were frequently supplanted by contemporary scientific ideas and medical procedures. It included contemporary topics like the role of natural productsand, emerging drug discovery trends in the field of Oncology, Forgotten Wisdom: Reviving the Legacy of Ethnomedicine through Plant-Based Remedies, Indianmedicinal plants used in hair problems, Ethnopharmacological application of medicinal plants to cure skin diseases and in folklore cosmetics among the major tribal communities of India and Antibacterial Activity Of Artabotrys Flower Oil On Atopic Dermatitis Pathogen Causes Skin Infection.
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A questionnaire evaluation of 486 hyperactive children (HA) (82% boys, aged 7-13 years and 18% girls, aged 8-13 years) showed that more than 60% of cases reported a positive behavioural response (i.e. increased problems) in relation to consuming or being exposed to synthetic colourings and flavourings, food and beverage preservatives, cow's milk and associated products, chemical detergents and perfume. In contrast, 172 sex- and age-matched control children (C) reported only 12% of cases responding to synthetic colourings and flavourings and chemical solvents. The main health problems reported by the 96% of hyperactive children affected by synthetic colourings and flavourings were persistent thirst problems, the development of eczema, ear and/or chest infections, and the production of excessive amounts of catarrh. Trace element measurements undertaken by inductively coupled plasma mass spectrometry showed that a low zinc and iron status is associated with hyperactive children when compared with control children for blood serum, urine and washed scalp hair (HA C). In many cases, hyperactive children also had very highly significant raised levels of aluminium, cadmium and/or lead (HA C), particularly in urine and washed scalp hair samples. Hyperactive children with a known behavioural response following the consumption of a beverage containing tartrazine, E ( n= 23), sunset yellow, E ( n= 12) 102 110 and amaranth, E ( n= 12) were given a dose of chemical food colour (50 mg) and their zinc 123 levels (blood serum and urine) and behavioural activity were monitored for 120 min. A sexand age-matched control group was also studied. Only hyperactive children showed a significant reduction in blood serum zinc levels and an increase in urinary zinc output following the consumption of E and E . Amaranth had no effect on their zinc status over 102 110 the study time period. There were no significant changes in the zinc levels for control children for all three chemical food colours. The main behavioural changes were observed in the hyperactive children given E and E . For the 23 children who consumed a tartrazine 102 110 beverage there were increased levels of overactivity ( n= 18 children), aggressive ( n= 16) and/or violent ( n= 4) activity, poor speech ( n= 2), poor coordination ( n= 12), and the development of asthma and/or eczema ( n= 8). Most of these were severe or moderate changes. Only one control child showed minor behavioural responses to tartrazine.
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Chemical carcinogenesis bioassays in animals have long been recognized and accepted as valid predictors of potential cancer hazards to humans. Most rodent bioassays begin several weeks after birth and expose animals to chemicals or other substances, including workplace and environmental pollutants, for 2 years. New findings indicate the need to extend the timing and duration of exposures used in the rodent bioassay. In this Commentary, we propose that the sensitivity of chemical carcinogenesis bio-assays would be enhanced by exposing rodents beginning in utero and continuing for 30 months (130 weeks) or until their natural deaths at up to about 3 years. Studies of three chemicals of different structures and uses-aspartame, cadmium, and toluene-suggest that exposing experimental animals in utero and continuing exposure for 30 months or until their natural deaths increase the sensitivity of bioassays, avoid false-negative results, and strengthen the value and validity of results for regulatory agencies. Government agencies, drug companies, and the chemical industry should conduct and compare the results of 2-year bioassays of known carcinogens or chemicals for which there is equivocal evidence of carcinogenicity with longer-term studies, with and without in utero exposure. If studies longer than 2 years and/or with in utero exposure are found to better identify potential human carcinogens, then regulatory agencies should promptly revise their testing guidelines, which were established in the 1960s and early 1970s. Changing the timing and dosing of the animal bioassay would enhance protection of workers and consumers who are exposed to potentially dangerous workplace or home contaminants, pollutants, drugs, food additives, and other chemicals throughout their lives.
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Charles River CD-1 mice were fed FD & C Red No. 3 in the diet at levels of 0.3, 1.0 and 3.0% in a long-term toxicity/carcinogenicity study. Each group consisted of 60 males and 60 females. Two concurrent control groups each of 60 males and 60 females received the basal diet. Maximum exposure was 24 months. The no-adverse-effect levels established in this study were 3.0% (an average intake of 4759 mg/kg/day) for male mice and 1.0% (1834 mg/kg/day) for female mice.
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Seven patients with allergic vascular purpura displayed hypersensitivity reactions after ingestion of azo dyes and benzoic acid compounds. All reacted with purpura after oral provocation with azo dyes. Three patients also developed purpura after ingesting benzoic acid compounds and four developed purpura after taking aspirin. Mild purpuric reactions after provocation are more easily revealed if the skin is pretreated with a nicotinic acid ester. The patients improved on a diet free from the additives. Beneficial effects, with decreased purpuric reactions after provocation, have also been observed from treatment with phenformin and ethylestrenol.
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Eight food dyes or commercial color mixtures certified for use in the United States were tested for their ability to transform in vitro a serial line of Fischer rat embryo cells previously reported to be a sensitive indicator of chemicals having carcinogenic potential. Malignant cell transformation was induced by a commercial mixture (G2024) of two of these dyes (Blue 1 and Yellow 5) and by Blue 2, Green 3 (one of two experiments) and Red 4. Food dyes Blue 1, Red 3, Yellow 5 and Yellow 6 did not induce cell transformation. One to 1.5 mg of each dye was injected into suckling LVG or Graffi hamsters which were monitored for tumor induction and/or death over a 330-day period. None of the non-transforming dyes (Blue 1, Red 3, Yellow 5, Yellow 6) or Green 3 induced a significant increase in tumor (mostly lymphoma) incidence or animal mortality. Three of the transforming dyes (Blue 2, Green 2024, Red 4) did increase tumor incidence and/or mortality in at least one strain of hamster. We conclude that the in vitro assay suggested that certain food dyes were carcinogens and that in vivo studies in hamsters supported this interpretation.
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Fifty-two patients with recurrent urticaria or angio-oedema and thirty-three controls have been provoked with five different food dyes and the preservatives sodium benzoate and 4-hydroxy-benzoic acid, as well as aspirin, sulphanilic acid and a placebo. The reaction was judged as positive in thirty-nine patients who developed urticaria within 14 h. Of these, thirty-five reacted to aspirin, twenty-seven to benzoic acid compounds and twenty-seven to azo dyes. The four patients who did not have urticaria after aspirin, reacted with urticaria to benzoic acid compounds, and three of them to azo dyes. No definite pattern for the reaction to the different azo dyes was seen. None had an urticarial reaction from sulphanilic acid, Patent Blue (a non-azo dye) or placebo. The doses of additives used in the provocation tests are easily exceeded in daily life by the consumption of foods and drugs. Recurrences of urticaria could be prevented through the avoidance of food and drugs containing azo dyes and preservatives.
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The rich capillary bed of the central nervous system (CNS) is impervious to protein. This generalization derives from two observed features of the cerebral capillary wall: (a) the tight junctions between contiguous endothelial cells comprise uninterrupted belts that arrest the passive, intercellular movement of protein and (b) the vesicles that bud off the endothelial cell membrane do not appear to carry protein across the cell from blood to perivascular tissue19. We would like to review briefly where and how this blood-brain barrier (BBB) to protein and peptide is circumvented in the normal and experimentally manipulated mammal. It will become apparent that in some vessels which are naturally permeable or rendered permeable experimentally, one or the other of both features is altered: the junctions are open and no longer tight and the endothelial plasmalemma of certain vessels is capable of vesicular transport. A third means of bypassing the barrier must still be considered as a strong suspicion rather than proven: fenestrae or round windows that perforate the attenuated endothelium of capillaries in a few specific regions are bridged by thin diaphragms that may be permeable to protein and peptide. A fourth bypass is one that we have just come to appreciate: the very axons of the neurons within the cerebral parenchyma. It is through the cytoplasm of these axons that large molecules can be brought from extracerebral, peripheral blood to neuronal cell bodies of the brain and spinal cord6.
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It is well known that synthetic food colours especially some azo dyes can provoke hypersensitivity reactions such as urticaria, angioneurotic oedema, and astma (Michaëlsson and Juhlin, 1973, Granholt and Thune, 1975). Natural food colours are scarcely investigated with respect to potential allergic properties. Annatto extract, a commonly used food colour in edible fats e.g. butter, has been tested in patients. Among 61 consecutive patients suffering from chronic urticaria and/or angioneurotic oedema 56 patients were orally provoked by annatto extract during elimination diet. Challenge was performed with a dose equivalent to the amount used in 25 grammes of butter. Twentysix per cent of the patients reacted to this colour 4 hours (SD: 2,6) after intake. Similar challenges with synthetic dyes showed the following results: Tartrazine 11%, Sunset Yellow FCF 17%, Food Red 17 16%, Amaranth 9%, Ponceau 4 R 15%, Erythrosine 12% and Brillant Blue FCF 14%. The present study indicates that natural food colours may induce hypersensitivity reactions as frequent as synthetic dyes.
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Thirty-seven azo, xanthene and triphenylmethane dyes including FD and C colors currently approved for use in the U.S.A. and a number of delisted food colors, were tested in the Salmonella/microsome system. In addition to direct plate tests with five tester strains (TA1535, TA100, TA1537, TA1538, TA98), the azo dyes were also assayed after chemical reduction to their component amines. Also, a selected group of azo dyes was subjected to liquid tests (both aerobic with microsomes and anaerobic) and to plate tests involving initial 16 h anaerobic incubations to facilitate microbial reduction of the azo bond. None of the presently listed FD and C colors was mutagenic in any of the test modifications. Among formerly listed colors only Butter Yellow (p-dimethylaminoazobenzene), a recognized animal carcinogen, was mutagenic in the aerobic liquid test. Several other azo dyes were either directly mutagenic, viz. Acid Alizarin Yellow R and Alizarin Yellow GG; required microsomal activation, viz. Acid Alizarin Red B and Methyl Red; or required chemical reduction and microsomal activation, viz. Acid Alizarin Violet N and Sudan IV. Of the non-azo dyes tested only two xanthene dyes appeared to be mutagenic, viz. 9-(2-sulfophenyl)-6-hydroxy-3-isoxanthenone and its 2,4,5,7-tetrabromo derivative.
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37 dyes including 3 anthraquinone, 22 azo; 5 xanthene, 5 fluorandiol, and 2 thioindigo dyes, were tested for mutagenic potential with the Salmonella/mammalian-microsome test. Two frame-shift histidine mutants (TA1537 and TA98) and two base-pair substituted histidine mutants (TA1535 and TA100) of Salmonella typhimurium were employed. Both the spot test and the plate-incorporation assay indicated that one azo dye, D&C Orange No. 17, was mutagenic with three of the bacterial test strains. The mutagenic response of D&C Orange No. 17 was depressed by the addition of the microsomal fractions from rat livers. Of the chemicals used to synthesize D&C Orange No; 17 was depressed by the addition of the microsomal fractions from rat livers. Of the chemicals used to synthesize D&C Orange No. 17, beta-naphthol was not mutagenic but 2,4-dinitroaniline was mutagenic to the same Salmonella strains as D&C Orange No. 17 . Dimethyl sulfoxide extracts of lipsticks of similar formula but without D&C Orange No. 17 were tested in the plate incorporation assay. Only those containing D&C Orange No. 17 were mutagenic and the dye was mutagenic at concentrations consumed in normal daily use.
Article
12 permitted food colours in use were screened for geno-toxicity. Mitotic gene conversion in Saccharomyces cerevisiae was used as the end-point. Each food colour was tested in stationary-phase as well as log-phase cells but without microsomal activation. These food colours did not cause any increase in mitotic gene conversion in diploid yeast BZ 34.
Article
A methodology for investigating genotoxicity of food colours using the fluctuation and DNA-repair assays with bacteria is described. In addition, a liquid repair test, developed to permit incorporation of microsomes and the quantitative estimation of cell viability, has been characterised with a number of positive control agents. Results obtained in these systems suggest that the food colour Red 2G induces repairable DNA damage and base-substitution mutation, but only in the presence of a rat-liver microsomal preparation. The significance of the data in the light of other toxicological information is discussed.
Article
1. Absorption and metabolism of 14C-labelled sunset yellow (FD & C Yellow No. 6), tartrazine (FD & C Yellow No. 5) and high molecular weight polymeric derivatives of the two azo dyes were compared in rats. 2. A trace to 1.5 percent of unchanged monomeric dyes was excreted in urine and bile during the first 24 h after dosing. No unchanged dye was absorbed after administration of the polymeric derivatives. 3. In animals dosed with sunset yellow and its polymer derivative, absorption of the azo-bound cleavage product 1-amino-2-naphthol-6-sulphonic acid was 8.5 and 6.9 percent, respectively, while absorption of the cleavage product sulphanilic acid was 37.4 and 0 percent, respectively. 4. In animals dosed with tartrazine and its polymer derivative, absorption of the cleavage product aminopyrazolone and its metabolites was 4.0 and 4.6 percent, respectively. 5. Azo bond cleavage did not appear to be decreased in the polymer derivatives. However, the sulphanilic acid moiety of both dyes remained attached to the polymer backbone, resulting in a 95 percent decrease in sulphanilic acid absorption with polymeric tartrazine. 6. Decreased absorption of unchanged dyes and certain metabolites with the stable, non-absorbed polymeric derivatives may be significant in developing non-sensitizing substitutes for these two commonly used food colourants.
Article
Oral administration of 50 mg tartrazine to 122 patients with a variety of allergic disorders caused the following reactions: general weakness, heatwaves, palpitations, blurred vision, rhinorrhoea, feeling of suffocation, pruritus and urticaria. There was activation of the fibrinolytic pathway as shown by reduction of plas-minogen with high pre-kallikrein and low kallikrein values. Reduction in complement activity (CH50) was seen in three out of sixteen reactions.
Article
Anaphylactic shock has been reported as a consequence of the injection or ingestion of a large number of substances used in everyday medical practice. The authors present here what they believe to be the first reported case of systemic anaphylaxis secondary to a standard enema preparation in a 15 yr old woman.
Article
Of 38 patients with chronic urticaria of unknown etiology who were evaluated for food and drug additive sensitivity, 53% (20/38) had urticaria for 1 yr or more. Total eosinophil counts were not elevated in most patients, and the frequency of atopy was found to be similar to that in a general population. Of these 38 patients, 10 (26%) had a personal history of aspirin intolerance, but elimination of aspirin did not relieve the urticaria. In a double-blind crossover challenge with 0.22 mg of tartrazine and a control, tartrazine sensitivity was found in 8% (3/38) of patients with chronic urticaria and 20% (2/10) of patients with aspirin intolerance.
Article
The 7-day LD50 values for Erythrosine BS were similar in both sexes of rats and mice at 6·7–7·4 g/kg after a single oral administration and 0·32–0·40 g/kg following an ip injection. Erythrosine BS was given to groups of 15 male and 15 female rats at dietary concentrations of 0 (control), 0·25, 0·5, 1·0 or 2·0% for 13 wk. There were no effects attributable to treatment on the rate of body-weight gain, food intake, results of haematological examinations, serum analyses or renal function tests. The main findings in the study were caecal distension at all treatment levels, an increase in thyroid weight and pigmentation of the kidney tubules. The pigmentation was found in both sexes at the highest level and in males given 0·5 or 1·0% Erythrosine BS. The no-untoward-effect level was 0·25% of the diet, equivalent to an intake of 160–170 mg/kg/day.
Article
The author reports a rapid improvement in behavior and learning abilities in HDL children following dietary management eliminating artificial food colors, flavors, and naturally occurring salicylates. Preliminary work in several research programs now under way confirms his observations which, if proven, will offer hope to many troubled children and parents
Article
Groups of 30 male and 30 female mice were fed diets containing 0·2, 0·4, 0·8 or 1·6% indigo carmine for 80 wk. A group of 60 male and 60 female mice served as controls. The treatment had no effects on the death rate, body-weight gain, organ weights or the results of the histopathological examination, including the incidence of tumours. There was a slight anaemia in mice given diets containing 0·8 or 1·6% indigo carmine. It is concluded that the feeding of indigo carmine to mice at dietary levels of up to 1·6% did not exert any carcinogenic effect. The no-untoward-effect level in this study was 0·4% of the diet.
Article
One-hundred and forty asthmatics were tested perorally with acetylsalicylic acid (ASA), and/or with the azo-colour tartrazine; a fall in PEF of more than 20% was accepted as a positive result. About one quarter of the patients displayed a positive reaction to one of the two tested agents. No significant correlation was found between the reactions of these, and the presence of atopy, nasal polyposis, sinusitis, rhinitis, sensitivity to cold air, the age at onset, duration of asthma, or history of sensitivity to alcoholic drinks. The history suggested sensitivity to ingested, possibly coloured, food and drink, in only about one third of the tartrazine-positive cases. The ASA provocation tests were mainly applied to patients with doubtful or negative histories of sensitivity to ASA-containing drugs. The frequency of cross-reactivity between the two tested agents was statistically significant; patients reacting to tartrazine were for the most part, also sensitive to ASA. Tests for sensitivity to analgesics and food additives should be conducted as a routine measure in asthmatics, and sensitive patients should be given information on suitable medication and dietary control.
Article
Free and bound non-sulphonated aromatic amines (NSAA) are determined in the food colours tartrazine, sunset yellow FCF and allura red. After reduction of the bound amines with sodium dithionite, the NSAA are extracted into chloroform, then transferred to aqueous acid solution, diazotized with sodium nitrite and coupled with 2-naphthol-3,6-disulphonic acid, disodium salt (R-salt). Reversed-phase ion-pair liquid chromatography and an absorbance detector at 512 nm are used to analyse the coloured derivatives. Samples of dyes were spiked with known amounts of aniline, 1-naphthylamine, 2- and 4-aminobiphenyl, 4-aminoazobenzene, benzidine, p-cresidine or 4-nitro-p-cresidine bound to R-salt. Recoveries averaged 90% in tartrazine, 65% in sunset yellow FCF and 71% in allura red. Detection limits ranged between 2 and 32 ng/g. A survey of 24 commercial samples revealed levels up to 520 micrograms/g total NSAA. The majority of NSAA are bound to the coupling compound during the manufacturing process and less than 7% remain as free amines in the dye.
Article
Solvent Yellow 14 is carcinogenic in rats, inducing neoplastic nodules of the liver, but is non-carcinogenic in mice. The present paper shows that Solvent Yellow 14 induces micronuclei in the bone marrow of rats after a single oral dose of 250 mg/kg and above. In mice, however, there was no increased incidence of micronuclei after single oral doses of up to 2000 mg/kg Solvent Yellow 14, thus reflecting the species specific carcinogenic effect of the compound. The structurally related azo dye FD & C Yellow No. 6 is noncarcinogenic to rats and mice and gave a negative result in both rat and mouse bone marrow micronucleus tests after a single oral dose of up to 2000 mg/kg. The rat bone marrow micronucleus test is therefore capable of discrimination between the carcinogenic and the non-carcinogenic azo dye. A negative result was obtained for Solvent Yellow 14 in an in vivo liver unscheduled DNA synthesis assay after oral doses up to 1000 mg/kg. This result demonstrates the inability of the two in vivo assays used to predict target organ specificity seen in the cancer bioassay.
Article
FD & C Red No. 40 (allura red) was fed to Charles River HaM/ICR (CD-1) (study A) and CD-1 outbred (study B) mice as a dietary admixture in two separate lifetime toxicity/carcinogenicity studies. Each study included an in utero exposure phase during which the colouring was fed at dietary concentrations of 0.0, 0.37, 1.39 or 5.19% throughout the mating, gestation and lactation periods. After random selection, the lifetime exposure phase was initiated using the same dietary concentrations with 50 mice/sex/group in study A and 100 mice/sex/group in study B. Exposure was for 104 wk in study A and 109 wk in study B. No compound-related adverse effects were observed. The no-observable-adverse-effect level in these studies was 5.19%; approximately 7300 and 8300 mg/kg body weight/day for male and female mice, respectively.
Article
Sprague-Dawley rats received dietary admixtures containing 0.0, 0.25, 1.0 or 4.0% FD & C Red No. 3 (25 rats/sex/group) in a three-generation reproduction study. Each generation was bred twice and breeders for subsequent generations were selected after weaning of the second mating from each generation. There were no compound-related adverse effects on reproductive indices and no gross anomalies were observed. The body weights of parents and pups were significantly reduced (P less than 0.05) in all generations at the 4.0% dietary concentration. Maternal body-weight gain during gestation was frequently reduced in the 1.0 and 4.0% groups. The conservative no-observed-adverse-effect level established in this study was 0.25% (approximately 149 and 255 mg/kg body weight/day for males and females, respectively).
Article
Tartrazine (FD & C Yellow No. 5) is an approved azo dye present in many drugs and food products. During the 1970s, many cases of tartrazine sensitivity were reported. This led to new regulations that required the listing of azo dyes on package inserts of drugs and on packages of food products. Tartrazine sensitivity is most frequently manifested by urticaria and asthma. Although azo dyes have been implicated in accentuating hyperkinetic syndromes, tartrazine is not considered an offender. Vasculitis, purpura and contact dermatitis infrequently occur as manifestations of tartrazine sensitivity. Cross-sensitivity in aspirin-sensitive and NSAID-sensitive patients may also occur. The mechanism of sensitivity is obscure and has been called pseudoallergic. Management consists mainly of avoidance of drugs and food products that contain tartrazine.
Article
FD & C Blue No. 1 was fed to Charles River CD rats and CD-1 mice as a dietary admixture in lifetime toxicity/carcinogenicity studies. The rat study was conducted with an in utero phase in which the compound was administered to the F0 generation rats (60/sex/group) at dietary concentrations of 0.0%, 0.0%, 0.1%, 1.0% or 2.0%. After randomly selecting the F1 animals, the lifetime phase was initiated at the same levels with 70 rats/sex/group, including two control groups. The maximum exposure times were 116 and 111 wk for males and females, respectively. The no-observed-adverse-effect levels are dietary concentrations of 2.0% for males (1072 mg/kg body weight/day), and 1.0% for females (631 mg/kg/day) based on a 15.0% decrease in terminal body weight and decreased survival in the high-dose females compared with the combined control groups. Charles River CD-1 mice (60/sex/group) were fed FD & C Blue No. 1 as a dietary admixture at levels of 0.0%, 0.0%, 0.5%, 1.5% or 5.0% in a lifetime toxicity/carcinogenicity study. The maximum exposure time was 104 wk for both males and females. No consistent, significant compound-related adverse effects were noted. The no-observed-adverse-effect level established in this study is a dietary concentration of 5.0% (7354 mg/kg/day and 8966 mg/kg/day for male and female mice, respectively.
Article
FD&C Red No.3 (erythrosine) has been used as a dye in foods, drugs and cosmetics since its approval by the US Department of Agriculture in 1907. In 1977 the Certified Color Manufacturers' Association (CCMA) initiated studies on FD&C Red No.3 including chronic toxicity and carcinogenicity studies in rats and mice. Data from the CCMA chronic studies revealed an increased incidence of thyroid follicular cell hyperplasia and adenomas in male rats that received 4% FD&C Red No.3 in the diet (2464 mg/kg/day) during life-time (30 months) following in utero exposure. In this report, results of published studies on the mutagenicity of FD&C Red No.3 are critically reviewed. Additional mutagenicity tests including Ames Salmonella/microsome assay, L5178Y TK+/- mouse lymphoma assay, mouse micronucleus test and mitotic recombination assay with yeast Saccharomyces cerevisiae strain D5 are described. These test results together with the literature review indicate that FD&C Red No.3 can be considered non-mutagenic across several genetic endpoints including gene mutation, chromosome aberrations, primary DNA damage and cell transformation. The results of the genotoxicity assessment generally exclude FD&C Red No.3 as a genotoxic initiator and suggest that some other mechanism is responsible for the increase in tumors.
Article
FD & C Red No. 40 was fed to Charles River CD (Sprague-Dawley) rats as a dietary admixture in a lifetime toxicity/carcinogenicity study. The study included a phase during which the colouring was administered to parental rats (30 of each sex per group) at concentrations of 0.0, 0.37, 1.39 and 5.19%, throughout the mating, gestation and lactation periods. The concurrent control group received the basal diet. After random selection of the first-generation rats, the lifetime phase was initiated using the same dietary concentrations with 50 rats of each sex per group. The maximum durations of exposure to the colouring were 118 and 121 for males and females, respectively. No compound-related adverse effects were observed, except for a reduction in body weight in high-dose females at the end of the study. The no-adverse-effect levels in this study were 5.19% (2829 mg/kg/day) for male rats, and 1.39% (901 mg/kg/day) for female rats.
Article
FD & C Red No. 3 was fed to Charles River CD rats as a dietary admixture in two long-term toxicity/carcinogenicity studies. The studies consisted of an in utero and an F1 phase. In the former, the compound was administered to five groups of the F0 generation rats (60 of each sex/group) at levels of 0.0, 0.0, 0.1, 0.5 or 1.0% ('original study') and 0.0 or 4.0% ('high-dose study'). The concurrent control groups received the basal diet. After random selection of the F1 animals, the long-term phase was initiated using the same dietary levels and 70 rats of each sex/group, including the three control groups. Rats were exposed for a maximum of 30 months. No compound-related effects were noted in the in utero phase. Mean body weights of the female F1 rats on 4.0% FD & C Red No. 3 (3029 mg/kg/body weight/day) were significantly lower than those of controls (P less than 0.01) throughout the study. Food consumption increased in all treated groups in a dose-related manner. There were no significant effects on the haematology, serum chemistry and urinalysis and no compound-related effects on survival. In male rats receiving 4.0% FD & C Red No. 3 (2464 mg/kg/day) thyroid weights were increased, with a mean weight of 92 mg compared to 44 mg for controls, and statistically significant increases in the incidence of thyroid follicular cell hypertrophy, hyperplasia and adenomas were recorded. A numerically increased incidence of thyroid follicular adenomas in female rats given 0.5, 1.0 or 4.0% FD & C Red No. 3 was not statistically significant. The no-observed-adverse-effect levels established in these studies were 0.5% (251 mg/kg/day) for male rats and 1.0% (641 mg/kg/day) for females.
Article
Charles River CD-1 mice were fed FD & C Yellow No. 5 in the diet at levels of 0.0, 0.0, 0.5, 1.5 or 5.0% in a long-term toxicity/carcinogenicity study. Each group consisted of 60 males and 60 females. Maximum exposure was 104 wk for both males and females. No consistent, significant compound-related adverse effects were noted. The no-observed-adverse effect level established in this study was 5.0% (8103 mg/kg/day and 9735 mg/kg/day for male and female mice, respectively.)
Article
FD & C Yellow No. 5 was fed to Charles River CD rats as a dietary admixture in two long-term toxicity/carcinogenicity studies. The studies were conducted with an in utero phase in which the compound was administered to the F0 generation rats (60/sex/group) at levels of 0.0, 0.0, 0.1, 1.0 or 2.0% ('original study') and 0.0 or 5.0% ('high-dose study'). The concurrent control groups received the basal diet. After random selection of the F1 animals, the long-term phase was initiated using the same dietary levels with 70 rats of each sex/group, including the three control groups. The maximum exposure to the colouring was 113 and 114 wk for males and females, respectively, in the 'original' study and 122 and 125 wk for males and females, respectively, in the 'high-dose' study. No compound-related effects were noted. The no-adverse-effect level found in this study was 5.0% in the diet providing an average intake of 2641 and 3348 mg/kg/day for male and female rats, respectively.
Article
Seventy‐two chemicals were tested for their mutagenic potential in the L5178Y tk ⁺ / ⁻ mouse lymphoma cell forward mutation assay, using procedures based upon those described by Clive and Spector (Mutat Res 44:269‐278, 1975) and Clive et al. (Mutat Res 59:61‐108, 1979). Cultures were exposed to the chemicals for 4 hr, then cultured for 2 days before plating in soft agar with or without trifluorothymidine (TFT), 3 μg/ml. The chemicals were tested at least twice. Significant responses were obtained with allyl isothiocyanate, p‐benzoquinone dioxime, benzyl acetate, 2‐biphenylamine HCl, bis(2‐chloro‐1‐methylethyl)ether, cadmium chloride, chlordane, chlorobenzene, chlorobenzilate, 2‐chloroethanol, chlorothalonil, cytarabine‐HCl, p,p′‐DDE, diazinon, 2,6‐dichloro‐p‐phenylenediamine, N,N‐diethylthiourea, diglycidylresorcinol ether, 2,4‐dimethoxy aniline‐HCl, disperse yellow 3, endosulfan, 1,2‐epoxyhexa‐decane, ethyl acrylate, ethyl benzene, ethylene thiourea, F D and C yellow Number 6, furan, heptachlor, isophorone, mercuric chloride, 4,4′‐methylenedianiline 2 HCl, methyl viologen, nickel sulfate‐6H 2 O, 4,4′‐oxydianiline, pentachloroethane, piperonyl butoxide, propyl gallate, quinoline, rotenone, 2,4,5,6‐tetrachloro‐4‐nitro‐anisole, 1,1,1,2‐tetrachloroethane, trichlorfon, 2,4,6‐trichlorophenol, 2,4,5‐trimetho‐xybenzaldehyde, 1,1,3‐trimethyl‐2‐thiourea, 1‐vinyl‐3‐cyclopetene dioxide, vinyl toluene, and ziram. Apart from 2‐biphenylamine‐HCl, 2‐chloroethanol, disperse yellow 3, ethylene thiourea, FD and C yellow number 6, phenol, and 1,1,2‐tetrachloroethane, rat liver S9 mix was not a requirement for these compounds. Chemicals not identified as mutagens were acid red, 11‐aminoundecanoic acid, boric acid, 5‐chloro‐o‐toluidine, coumaphos, cyclohexanone, decabromodiphenyl oxide, di(2‐ethylhexyl)adipate, ferric chloride, fluometuron, melamine, monuron, phenesterin, phthalimide, reserpine, sodium dodecyl sulfate, 4,4‐sulfonyldianiline, tetrachloroethylene, and zearalenone. The assay was incapable of providing a clear indication of whether some chemicals were mutagens; these were benzyl alcohol, 1,4‐dichlorobenzene, phenol, succinic acid‐2,2‐dimethyl hydrazide, and toluene.
Article
Of 220 children referred for suspected 'hyperactivity', 55 were subjected to a 6 week trial of the Feingold diet. Forty (72.7%) demonstrated improved behaviour and 26 (47.3%) remained improved following liberalization of the diet over a period of 3-6 months. The parents of 14 children claimed that a particular cluster of behaviours was associated with the ingestion of foods containing synthetic colourings. A double-blind crossover study, employing a single-subject repeated measures design was conducted, using eight of these children. Subjects were maintained on a diet free from synthetic additives and were challenged daily for 18 weeks with either placebo (during lead-in and washout periods) or 50 mg of either tartrazine or carmoisine, each for 2 separate weeks. Two significant reactors were identified whose behavioural pattern featured extreme irritability, restlessness and sleep disturbance. One of the reactors did not have inattention as a feature. The findings raise the issue of whether the strict criteria for inclusion in studies concerned with 'hyperactivity' based on 'attention deficit disorder' may miss children who indicate behavioural changes associated with the ingestion of food colourings. Moreover, for further studies, the need to construct a behavioural rating instrument specifically validated for dye challenge is suggested.
Article
Charles River CD rats (20 pregnant rats/group) received by gavage on days 6-15 of gestation 0.5% Methocel (controls, A, B and C), retinoic acid at 7.5 mg/kg/day or FD & C Blue No. 2 in doses of 25, 75 or 250 mg/kg/day. Pregnant Dutch belted rabbits (ten pregnant does/group) received by gavage on days 6-18 of gestation 0.5% Methocel (controls A, B and C), thalidomide at 150 mg/kg/day or FD & C Blue No. 2 in doses of 25, 75 or 250 mg/kg/day. All animals were observed twice daily during gestation for signs of toxicity. The animals were killed 1 day before term and appropriate maternal and foetal parameters were evaluated. There were no consistent, significant compound-related adverse effects on any of these parameters. Foetal malformations occurred in both positive control groups. Under the conditions of this study, FD & C Blue No. 2 did not exert any teratogenicity or other developmental toxicity in either rats or rabbits.
Article
In a three-generation reproduction study, groups of ten male and 20 female Charles River CD rats were fed FD & C Blue No. 2 at dietary levels providing intakes of 0.0, 2.5, 25, 75 and 250 mg/kg body weight/day. Slightly bluish-coloured fur was noted in rats at the 250-mg/kg/day dose level and bluish-green-coloured faeces were produced by rats in the 75- and 250-mg/kg/day groups. The gestation, viability and lactation indices of all litters were comparable for the control and treated groups. The fertility indices for female rats in the 2.5- and 25-mg/kg/day groups were significantly lower than those for control females in the case of the F2 litters. However, there was no reduction in the female fertility indices for the F2 litters at the two higher dosage levels, nor for the F1 and F3 litters at any dosage level. Although fertility indices were reduced for some groups of male rats in the F2b and F2c litters, these changes were not considered to be compound-related. Examination of the ovaries and uteri of all dams killed on day 19 of gestation of the F2c and F3c litters revealed no gross anatomical abnormalities. No unusual changes were observed in the stillborn pups or in pups dying during the study. There were no compound-related gross or microscopic pathological lesions in any of the F1 or F3a rats that were killed and necropsied, and no compound-related organ-weight variations were recorded in the F1 parental rats.
Article
The vicissitudes of the studies of the permeability of the blood-CSF barrier during fetal and perinatal life illustrate how a subject of apparent great complexity was solved long ago by simple and highly reproducible experiments. The administration of dyes into newborn animals clearly suggested that the barrier was somehow deficient during fetal development, yet this claim was later disavowed and only in recent years has the original suggestion been fully confirmed. The outcome is the present awareness that during development the brain is particularly sensitive to environmental toxic agents which may gain access into the fetal bloodstream from the maternal circulation. The placenta, therefore, becomes the real barrier between the environment and the brain via the mother. The high rate of transfer of plasma proteins into fetal CSF and their presence in brain tissues also illustrates the need to reanalyse the role that the CSF plays during the early stages of CNS development.
Article
FD & C Blue No. 2 was fed to rats in the diet in a long-term toxicity/carcinogenicity study. The study included an in utero phase in which the compound was administered to groups of 60 male and 60 female Charles River CD albino rats at levels of 0.5, 1.0 and 2.0%. Two concurrent control groups, each containing 60 rats of each sex, received the basal diet. After random selection of the F1 animals, the long-term phase was initiated at the same dietary levels, with 70 rats of each sex in each dose group and in each of two control groups. Maximum exposure was 30 months. No consistent compound-related biologically adverse effects were noted. There were random statistically significant differences from the controls with respect to body weight, food consumption and clinical chemistry tests. Food consumption by the test groups showed a dose-related increase. This was probably due to the non-nutritive character of the colouring. A statistically significant increase in gliomas in the high-dose male rats was not found to be biologically significant, since none of the criteria for determining the neurocarcinogenic potential of chemical substances was met. The overall brain-tumour incidence in this study was within the range typical for 2-yr-old CD rats. Under the conditions of this study, FD & C Blue No. 2 did not produce evidence of any toxicity, including carcinogenicity.
Article
Charles River CD-1 mice were fed FD & C Blue No. 2 in the diet levels of 0.5, 1.5 and 5.0% in a long-term toxicity/carcinogenicity study. Each group consisted of 60 males and 60 females. Two concurrent control groups each of 60 males and 60 females received the basal diet. Maximum exposure was 23 months. No consistent compound-related or statistically significant biologically adverse effects were noted.
Article
Recombinationless mutant cells ofBacillus subtilis are more sensitive to the cell-killing action of typical chemical mutagens, such as ethyl methanesulfonate, hydroxylamine, mitomycinC,N-methyl-N′-nitrosoguanidine or4-nitroquinoline-N-oxide than are the wild-type bacteria. Based on this relation, a simple method was devised for screening new chemical mutagens by examining their increased lethal action on Rec− over Rec+ bacteria instead of assessing their mutagenic capacities directly. We call this method “rec-assay”. When it was applied to a number of dyes, phloxine was found to be positive. Though this rec-assay procedure did not show the mutagenicity of phloxine directly, successive experiments usingE. coli cells showed that this dye really was mutagenic. Thus a correlation between the rec-assay result and the genetic data was confirmed. The rec-assay was also carried out in the peritoneal cavity of mice that had received intramuscular injections of phloxine.
Article
Electron microscopic observations of the parotid gland and the pancreas were done on rats with acute pancreatitis, obstructive jaundice, ileus or peritonitis produced as reported previously. In acute pancreatitis the ultrastructural changes noted in the parotid acinar cell were an irregular arrangement of the acinar cells associated with atrophy, decrease in number of secretory granules, dilatation of cisternae of the granular endoplasmic reticulum and appearance of lipid droplets. In other sets of experiments, however, these ultrastructural changes were not noted; the appearance of lipid droplets was the only finding in the obstructive jaundice produced by ligation of common bile duct at the hilar portion of liver. The ultrastructural features of the parotid acinar cells in the experimentally produced pancreatitis were compatible with histological findings previously reported. It is conceivable that the ultrastructural changes, except appearance of lipid droplets, in the parotid gland are induced by pancreatitis. The results of the present study provide additional evidence for the close relation between pancreas and parotid gland.
Article
Erythrosine (FD & C Red No. 3) was administered to male and female Osborne-Mendel rats either by intubation twice weekly for 85 wk or continuously in the diet for 86 wk. No consistent differences in red blood cell counts, haematocrit, haemoglobin, reticulocyte counts or other indications of anaemia were observed. Increased values for protein-bound iodine were attributed to circulating erythrosine in the blood serum; these values had returned to normal 16 wk after erythrosine administration ceased. Thyroxine-iodine levels were not affected in treated rats. No gross nor microscopic pathology was attributed to administration of this dye.