Background: Recently progressive using of synthetic food additives increase the attention paid to its benefit and toxicity in the food specially for young. One of these additives is artificial azo dyes tartrazine. Aims: To provide an outline of the evidence existing on the beneficial and side effect of food additive with special reference to tartrazine on different organ health. Methods: Relevant databases were update search. The studies included description of the types of food additives and products containing tartrazine and focused on the effect of tartrazine on, liver, kidney function, lipid proﬁle, oxidative stress biomarkers, nervous system, hyperactivity, behavior, cancer, reproductive and developmental toxicity and some bioelement levels of tartrazine. Results: Several studies were identified and some investigating whether advantage and disadvantage of tartrazine were assessed. Summary of indications on potential harmful effects of tartrazine on, liver, renal function, lipid profiles, behavior, and carcinogenicity have been provided and forthcoming research advices are outlined. This review gives a broad evaluation of the safety and various toxicity effect of tartrazine. It could be concluded that there is a need for professional assistance for consumers regarding food safety issues.
A wide range of food additives, running into more than 2,500 items used to enhance foods are a consequence of industrialization and the development of food processing technology. A food additive is permitted for human consumption after studying its acute, subacut and chronic toxicity. Nevertheless, post-marketing surveillance of its effects must be kept for a long time. Information concerning the safety of long term use of such chemicals, their combined effect and mutability within the organism is scarce.
Aims and concerns of the review are to evaluate the effect of food coloring, as food additives; on hepatic function, lipid profile, and biomarkers of oxidative stress in blood and different tissue.
Search strategy: A structured literature review was conducted in PubMed, ScienceDirect and google schoolar to recognize studies available that described on the association between safty and hazard effect of tartrazine in experimental and clinical studies. The search sequence include the importance, disadvantages, types of food additives and products containing tartrazine. Moreover focused on the effect of tartrazine on albumin binding, liver enzymes, kidney function, lipid proﬁle, oxidative stress biomarkers, nervous system, hyperactivity, behavior, cancer , reproductive and developmental toxicity of tartrazine. Total titles and abstracts were screened at the beginning, followed by a full-text assessment of appropriate original and review manuscript. Citations of recently and important published studies and reviews were scanned for related articles that were not known through the initial electronic search.
3. Food additives:
3.1-Importance and disadvantages of food additives:
Many people consume various food additives every day, what is the advantage and disadvantage. Food additives has an important effect in today's abundant and nutritious food source, they permit our developing population to appreciate a diversity of safe, nutritious and delicious foods over the year. Food additives make a different of beneficial purposes in the foods.
However the disadvantage of food additives may be due to several metabolites, such as nitrous compounds, have been found to be carcinogens. Toxicity or benefit depends on to what extent food components affect absorption, excretion or the metabolism as a whole. Because there may be interaction among different substances, the definition of adequate safety limits for human consumption is further compounded.
Food additives sometimes destroy vitamins in food (adding Caramel is found to cause deficiency of vitamin B6), used to make bad quality food look good and cause allergy to many people like diarrhea, skin irritation, stomach disorders, vomiting or increase in the body heat. Also it may destroy the nutritional value of food.
Many food colorings have been banned due to their propensity to cause cancers and organ damage. Tartrazine as a food additive has been proven to cause many different side-effects and allergic reactions in people. These can include: anxiety, migraines, asthma attacks, blurred vision, eczema, other skin rashes and thyroid cancer.
3.2-Types of food additives:
Food additives can be divided into six major categories: preservatives, nutritional additives, flavoring agents, coloring agents, texturizing agents and miscellaneous agents. Examples of widely used food products containing target food additives and frequently consumed by children provided in table (1). The food additives include:
Preservatives are added to prolong the shelf life of foods. There are three types of preservatives: Antimicrobials: Those prevent microbial growth, which can cause life threatening illnesses such as salmonellosis or botulism e.g. benzoic acid, ascorbic acid and propionic acid. These preservative can be used in cheeses, margarine and dressings, bakery products and dried fruit preparations.
Antioxidants: Oxidation of food is a destructive process, causing loss of dietary value and changes in chemical composition and biochemical effects. Antioxidants are added to oils containing unsaturated fats which are more susceptible to oxidation. to prevent them from becoming rancid, slow the rate of oxidation and prolong food life. Synthetic and natural antioxidants give comparable performance and they are often used in combination. Some important antioxidants include Vitamin C and E, Citric acid, butylated hydroxytoluene (BHT) and Butylated hydroxyanisole.
Antibrowning: Antibrowning is added to fruits vegetables to prevent enzymatic browning. e.g. alpha tocopherol.
3.2.2- Nutritional additives:
They are added to increase the nutritional value of the food. These additives include vitamins, amino acids and minerals.
3.2.3- Flavoring agents:
Flavoring agents comprise the greatest number of additives used in foods. There are three major types of flavoring agents: a) Sweeteners: These are substances that have a strong sweet taste but little or no caloric values. They are therefore useful for diabetics include saccharin, sorbitol and aspartame.
b) Synthetic flavoring enhancers: They are used in general at very low level and they are synthetic mainly esters; aldehydes and ketons.
c) Natural flavoring enhancers: They are used to modify the flavor of food without contributing any flavor on, their own, for example monosodium glutamate (MSG) and nucleotides such as disodium guanylate.
3.2.4- Texturizing agents:
These agents are used to add or modify the overall texture or mouthful of food products. Emulsifiers and stabilizers are the primary additives in this category Emulsifiers include natural substances such as lecithin and mono-and diglycerides as well as several synthetic derivatives. The primary role of these agents is to allow flavors and oils to be dispersed throughout food products. Stabilizers, include several natural gums such as carragreenan as well as natural and modified starches. These additives have been used for several years to provide the desired texture in products such as ice cream and are now also used in both dry and liquid products. They are also used to prevent evaporation and deterioration of volatile flavor oils.
3.2.5- Coloring agents:
They are added to enhance visual appeal of food products. Some of these substances are derived from the natural colors, such as carotene and chlorophyll; others are synthetic such as indigotine, allura red, tartrazine and carmoisine.
Color additives exempt from certification are used for a wide variety of purposes in foods, drugs and cosmetics (Van-Bever, 1989). Although all color additives are alike in terms of the FDA's regulatory definition, they are regulated in two classes; the certified (synthetic) color additives, and the color additives exempt from certified (natural) .
Whey we focus on using tartrazine , because its extensive usage, provide of colour to colourless foodstuff, make the food more attractive
4. Research on Tartrazine:
Tartrazine known as E102 or FD&C Yellow 5 or C.I. 19140 is an artificial lemon yellow azo dye used for coloring of the food. It is derived from coal tar. It is water soluble and its sstructure displayed in Fig. (1).
4.1 - Products containing tartrazine:
4.1.1- Foods: Several foods have tartrazine in different quantities, relying on the industrialist or the cook administrator. Nowadays, the tendency is to prevent its addition or its replacement with a non- synthetic coloring material like annatto, malt color, or beta carotene. Foodstuffs containing tartrazine usually comprise sweetmeat, cotton candy, soft drinks, flavored chips (Nachos and Doritos), cereals (muesli and corn flakes), cake combinations, soups, sauces, some rice, ice cream, candy, chomping gum, marzipan, jelly, jam, gelatins, mustard, marmalade, yogurt, noodles, certain brands of fruit mash, fruit pleasant, chips and many expediency foods accompanied with lemon, glycerin and honey products, soft drinks (Mountain Dew), energy drinks, prompt desserts, and some product containing tartrazine in Figure (2) .
4.1.2- Non-food products: Tartrazine may found in non food products like, soaps, cosmetics, shampoos and other hair products, moisturizers, crayons and stamp dyes.
4.1.3- Medications: Some medical preparations contain tartrazine such as vitamins, antiacids, medicinal capsules and certain prescription drugs.
Accumulating research have been performed in tartrazine and its effect on the health
4.2- Metabolism and biological Effects of Tartrazine:
Because it is a nitrous derivative (azo class), it reduced in the organism to an aromatic amine which is highly sensitizing. Its main metabolite identified to date is sulfanylic acid. Tartrazine is a nitrous derivative and is known to cause allergic reactions such as asthma and urticaria, as well as having been the focus of studies on mutagenesis and carcinogenesis due to its transformation into aromatic amine sulfanilic acid after being metabolized by the gastrointestinal microflora (Moutinho et al., 2007) and possibly by mammalian azo reductase in the hepatic or intestinal wall after consumption (Chequer et al., 2011). When these azo dyes are reduced totally into aromatic amines, it oxidized to N-hydroxy derivatives by the enzymatic system of P450 (Demirkol et al., 2012). This mechanism of biotransformation take place in many species including humans (Chequer et al., 2011), which is responsible for various disorders including anemia, pathological lesions in the brain, liver, kidney and spleen, allergic reactions tumor and cancer
However Tartrazine does not have a potential to induce benign or malignant neoplasias. Moreover, Tanaka (2006) did not demonstrate any adverse effects of Tartrazine on neurobehavioral development and harmful effects on reproductive parameters were also not demonstrated at dose of 773 and 1225 mg Tartrazine/kg bw/day for males and females, respectively. In the previous evaluations there were no indications of Tartrazine-related adverse effects on reproduction.
Reactive oxygen species (ROS) such as superoxide anion, hydroxyl radical and H2O2 could be produced in the metabolism of nitrosamines and increase oxidative stress (Banasal et al., 2005).
4.3- Tartrazine and sensitivity:
Either consumption or cutaneous contact to a material enclosing tartrazine can produce symptoms of sensitivity. A variety of immunologic responses have been attributed to tartrazine ingestion, comprising nervousness, migraines, clinical depression, general weakness, purple skin spots, and sleep disruption Some claim to experience symptoms of tartrazine sensitivity even at very minor doses, and until 72 hours following the exposure. In children, asthma attacks and hives have been claimed, including supposed links to thyroid tumors, chromosomal damage, hives, and hyperactivity. Particular investigators have related tartrazine to infantile obsessive-compulsive disturbances and hyperactivity.
Some common food additives include tartarzine, monosodium glutamate have been suggested
as risk factors for exacerbations of asthma. Tartarzine which is also used in many medications, and may increase asthma severity only in a few susceptible individuals, while MSG may exacerbate asthma, more rigorously (Romieu, 2005).
Tartrazine, among other examined food additives, increased sulphido-leukotriene production by peripheral leucocytes in patients with proven food intolerance towards food additives (in the form of atopic dermatitis). This process may be a pathophysiological mechanism involved in food additive mediated aggravation of atopic dermatitis (Worm et al. 2001).
In humans, adverse reactions such as urticaria and vasculitis after Tartrazine intake have been recorded in a number of studies. EFSA Panel (2009) concluded that Tartrazine appears to be able to elicit intolerance reactions in a small fraction of the exposed population and noted that sensitive individuals may respond at dose levels within the ADI.
However the Brazilian Sanitary Surveillance Agency (ANVISA) issued a consultation about the possibility of distributing a label warning the cause of exacerbations of asthma, allergic rhinitis and urticaria in atopic patients of food and drugs containing tartrazine. While, Pestana et al., 2010 reported that there were no statistical differences between placebo and drug in cutaneous, respiratory or cardiovascular aspects and concluded that in a group of atopic subjects with allergic rhinitis, asthma, urticaria or pseudo-allergic reactions to non-steroidal anti-inflammatory drugs, the administration of 35 mg of the tartrazine dye did not precipitate any kind of significant cutaneous, respiratory or cardiovascular reactions when compared to placebo.
4.4. Effect of tartrazine in albumin binding:
Tartrazine could lead to conformational and some microenvironmental changes of both bovine serum albumin and human serum albumin, which may affect the physiological functions of SAs. This provides important insight into the mechanism of toxicity of tartrazine in vivo (pan et al., 2011).
The synchronous fluorescence experiment revealed that tartrazine binds into the hemoglobin central cavity, and this was verified using a molecular modeling study (Li et al., 2014).
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