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  1. Jabeen 2013
  2. Yellow 6 2011
  3. Kamel 2011
  4. Gao 2011
  5. Shimada 2010
  6. Mpountoukas 2010
  7. Lechner 2010
  8. Amin 2010
  9. Hashem 2010
  10. Dalal 2009
  11. EFSA 2009
  12. Mehedi 2009
  13. Mizutani 2009
  14. Peng 2009
  15. Poul 2009
  16. Allura Red
  17. Elhkim 2007
  18. Moutinho 2007
  19. Lau 2006
  20. Tanaka 2005
  21. Lucarelli 2004
  22. Alsolaiman 2003
  23. Federal Register 2003
  24. FDA 2003
  25. Sasaki 2002
  26. Granville 2001
  27. Piruzian 2001
  28. Tanaka 2001
  29. Tsuda 2001
  30. Ashida 2000
  31. Boutilier 2000
  32. Maloney 2000
  33. Zillich 2000
  34. Lancaster 1999
  35. Huang 1998
  36. Koutsogeorgopoulou 1998
  37. MMWR 1998
  38. Taylor 1998
  39. Abdel 1997
  40. Aboel-Zahab 1997
  41. Dees 1997
  42. Pediatrics 1997
  43. Bhatia 1996
  44. Kumar 1996
  45. Rao 1996
  46. Reyes 1996
  47. Tanaka 1996
  48. Corder 1995
  49. Lowry 1994
  50. Sweeney 1994
  51. Bamforth 1993
  52. Kumar 1993
  53. Prival 1993
  54. Tanaka 1993
  55. Wuthrich 1993
  56. Chung 1992
  57. Tanaka 1992
  58. el-Saadany 1991
  59. Kumar 1991
  60. Dipalma 1990
  61. Rosenkranz 1990
  62. D'Souza 1987
  63. Levitan 1984
  64. Smith 1984
  65. Chung 1983
  66. Vorhees 1983
  67. Alvarez Cuesta 1981
  68. Chung 1981
  69. Hedman 1981
  70. Augustine 1980
  71. Gallagher 1980
  72. Ishihara 1979
  73. Lafferman 1979
  74. Logan 1979
  75. Ceserani 1978
  76. Chung 1978
  77. Ershoff 1977
  78. Levitan 1977
  79. Sobotka 1977
  80. Lethco 1966
  81. Jones 1964


Basic Research on Food Dyes

Research Menu Page ||| Last update 4/23/2015


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  • Abdel Aziz AH, Shouman SA, Attia AS, Saad SF, A study on the reproductive toxicity of erythrosine in male mice. Pharmacol Res 1997 May;35(5):457-62
    "... The potential adverse effects of erythrosine (ER, FD & C Red No. 3) on the spermatogenesis process were investigated in adult mice. ... sperm count as well as the percentage of motile sperms were significantly inhibited by about 50% and 57% respectively. Moreover, ER was shown to disrupt the normal morphology of the sperm head. ...it increased the incidence of sperms with abnormal head by about 57% and 65% respectively. The induced increase in sperm abnormalities could enhance the spermatogenic dysfunction and germ cell mutagenicity. These findings indicate that ER in the used doses has a potential toxic effect on spermatogenesis in mice and in turn, it may affect its testicular function and reproductive performance."

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  • Aboel-Zahab H, et al., Physiological effects of some synthetic food colouring additives on rats. Boll Chim Farm 1997 Nov;136(10):615-27
    " Three different synthetic chocolate colourant agents (A, B and C) were administered to healthy adult male albino rats for 30 and 60 day periods to evaluate their effects ... Ingestion of colourant C (brown HT and indigocarmine) significantly decreased rat body weight, serum cholesterol and HDL-cholesterol fraction, while, T4 hormone, liver RNA content, liver enzymes (S. GOT, S. GPT and alkaline phosphatase), total protein and globulin fractions were significantly elevated. Significant increases were observed in serum total lipids, cholesterol, triglycerides, total protein, globulin and serum transaminases in rats whose diets were supplemented with chocolate colours A and B (sunset yellow, tartrazine, carmoisine and brilliant blue in varying concentrations). ... haemoglobin concentrations and red blood cell counts were significantly decreased in the rats who were administered food additives A and B. ... Congested blood vessels and areas of haemorrhage in both liver and renal sections were revealed in those rats who were given colourants B and C. ..."

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  • Allura Red E 129
    Monograph, full text, undated; date estimate after 2007.

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  • Alsolaiman MM, Howard L., FD&C Blue Dye No. 1 and Blue Nail Discoloration: Case Report, Nutrition. 2003 Apr;19(4):395-6.
    "We report the clinical observation of blue nails in a severely ill patient receiving enteral feeding colored by FD&C blue dye no. 1. The dye was discontinued, and the blue discoloration slowly moved distally and disappeared after 4 wk."

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  • Alvarez Cuesta E, Alcover Sánchez R, Sainz Martín T, Anaya Turrientes M, García Rodríguez D., Pharmaceutical preparations which contain tartrazine. Allergol Immunopathol (Madr). 1981 Jan-Feb;9(1):45-54.
    "Allergic reactions to food colors have been known since 1958. Reactions to tartrazine, our example, include generalized pruritus, urticaria, angioedema, paresthesias, vomiting, migraine, rhinorrhea and nasal obstruction, coughing, asthma attacks and purpura [bruising]. Many patients who are allergic to antiinflammatory drugs such as acetyl-salicylic acid [aspirin] and indomethacin show cross-reaction to tartrazine. Doses producing these reactions range from minimal amounts up to 750 mg. Symptoms appear after periods of time ranging from minutes to 6 to 14 hours. In view of these facts (some of which represent a threat to the patient's life), additives, colouring matter, etc, do not usually appear in product labels or specifications, or in handbooks or catalogues used in practice. We drew up a list of drugs which may contain food dyes and coloring matter, yellow No. 5. A letter was written to 233 laboratories of which 159 (68%) replied. 72 (45%) in the affirmative and 87 (55%) in the negative, 74 (32%) did not reply."

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  • Amin KA, Abdel Hameid H 2nd, Abd Elsttar AH., Effect of food azo dyes tartrazine and carmoisine on biochemical parameters related to renal, hepatic function and oxidative stress biomarkers in young male rats. Food and Chemical Toxicology 2010 Oct;48(10):2994-9. Epub 2010 Aug 3.
    "... Tartrazine and carmoisine were administered orally in two doses, one low and the other high dose for 30 days followed by serum and tissue sample collection for determination of ALT, AST, ALP, urea, creatinine, total protein, albumin, lipid profile, fasting blood glucose in serum and estimation of GSH, catalase, SOD and MDA in liver tissue in male albino rat. Our data showed a significant increase in ALT, AST, ALP, urea, creatinine total protein and albumin in serum of rats dosed with tartrazine and carmoisine compared to control rats and these significant change were more apparent in high doses than low, GSH, SOD and Catalase were decreased and MDA increased in tissue homogenate in rats consumed high tartrazine and both doses of carmoisine. We concluded that tartrazine and carmoisine affect adversely and alter biochemical markers in vital organs e.g. liver and kidney not only at higher doses but also at low doses."

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  • Ashida H, Hashimoto T, Tsuji S, Kanazawa K, Danno G., Synergistic effects of food colors on the toxicity of 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) in primary cultured rat hepatocytes. Journal of Nutritional Science and Vitaminology. (Tokyo) 2000 Jun;46(3):130-6
    " ... the in vitro treated food-color mixture itself showed cytotoxicity: ... The food-color mixture enhanced cytotoxicity of Trp-P-1 obviously. We then investigated the effects of in vivo-dosed food additives or food colors on Trp-P-1-caused toxicity. Hepatocytes were isolated and cultured from rats fed a diet containing a mixture of food additives or a mixture of food colors with half the amount of their respective acceptable daily intake for 4 wk. Trp-P-1 was administered to the hepatocytes at various concentrations for 12 h. ... These results suggest that the daily intake of artificial food colors may impair hepatic functions such as gluconeogenesis and ureogenesis, when dietary carcinogens are exposed to the liver cells."

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  • Augustine G, Levitan H. Neurotransmitter Release from a Vertebrate Neuromuscular Synapse Affected by a Food Dye, Science Magazine, March 28, 1980, Vol. 207, pp. 1489-90
    "...FD&C No.3 ... produced an irreversible, dose-dependent increase in neurotransmitter release ... These results suggest that erythrosine might prove a useful pharmacological tool for studying the process of transmitter release, but that its use as a food additive should be re-examined."

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  • Bamforth KJ, Jones AL, Roberts RC, Coughtrie MW, Common food additives are potent inhibitors of human liver 17 alpha-ethinyloestradiol and dopamine sulphotransferases. Biochem Pharmacol 1993 Nov 17;46(10):1713-20
    "... dopamine sulphotransferase (ST) activity was inhibited strongly by (+/-)-catechin, (+)-catechin, octyl gallate, tartrazine [Yellow #5] and vanillin. Sulphation of the xenobiotic steroid 17 alpha-ethinyloestradiol (EE2) was inhibited by vanillin, erythrosin B and octyl gallate [anti-oxidant used in margarine]. ... Vanillin was found to inhibit 50% of liver EE2 ST activity ..."

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  • Bhatia MS, Allergy to tartrazine in alprazolam. Indian J Med Sci 1996 Aug;50(8):285-6
    "Allergy to tartrazine-containing psychotropic medication (especially antidepressants) had been reported. 20 patients of apparent allergy to tartrazine-containing alprazolam brands in 480 patients exposed to the dye are described. Rechallenge with non tartrazine-containing alprazolam brands did not produce the similar allergic reactions."

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  • Boutilier RG, Murray SK, Walley VM. Green colon: an unusual appearance at autopsy. Arch Pathol Lab Med. 2000 Sep;124(9):1397-8.

    Two case studies of patients who had green discoloration of their colons at autopsy. Patients had been fed by tube and the feed was colored with Blue 1 - sometimes in a ratio of color : food of 1 : 10.

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  • Ceserani R, Colombo M, Robuschi M, Bianco S., Tartrazine and prostaglandin-system. Prostaglandins Med 1978 Dec;1(6):499-505
    " Tartrazine, a dye largely employed for colouring foods, drinks, drugs and cosmetics, induces in some aspirin-sensitive subjects a bronchoconstriction similar to that caused by aspirin and other nonsteroidal anti-inflammatory drugs. . . . Preliminary experiments on aspirin asthmatic patients treated or not with tartrazine are discussed. "

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  • Chung KT, Fulk GE, Andrews AW., Mutagenicity testing of some commonly used dyes. Applied and Environmental Microbiology, 1981 Oct;42(4):641-8.
    " Seventeen commonly used dyes and 16 of their metabolites or derivatives were tested ... Nonmutagenic azo dyes were allura red, amaranth, ponceau R, ponceau SX, sunset yellow, and tartrazine. Miscellaneous dyes not mutagenic were methyl green, methyl violet 2B, and nigrosin. . . "

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  • Chung KT. The significance of azo-reduction in the mutagenesis and carcinogenesis of azo dyes. Mutation Research 1983 Apr;114(3):269-81
    " Azo dyes are widely used . . . The extent of such use is related to the degree of industrialization. Since intestinal cancer is more common in highly industrialized countries, a possible connection may exist between the increase in the number of cancer cases and the use of azo dyes. Azo dyes can be reduced to aromatic amines by the intestinal microflora. The mutagenicity of a number of azo dyes is reviewed in this paper. . . "

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  • Chung KT, Stevens SE Jr, Cerniglia CE. The reduction of azo dyes by the intestinal microflora. Critical Reviews in Microbiology. 1992;18(3):175-90
    " Azo dyes . . . are metabolized to aromatic amines by intestinal microorganisms. Reductive enzymes in the liver can also catalyze the reductive cleavage of the azo linkage to produce aromatic amines. However, evidence indicates that the intestinal microbial azoreductase may be more important than the liver enzymes in azo reduction. In this article, we examine the significance of the capacity of intestinal bacteria to reduce azo dyes and the conditions of azo reduction. . . . The azoreductase activity in a variety of intestinal preparations was affected by various dietary factors such as cellulose, proteins, fibers, antibiotics, or supplementation with live cultures of lactobacilli."

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  • Chung KT, Fulk GE, Egan M. Reduction of azo dyes by intestinal anaerobes. Applied and Environmental Microbiology, 1978 Mar;35(3):558-62
    " Reduction of seven azo dyes (amaranth, Ponceau SX, Allura Red, Sunset Yellow, tartrazine, Orange II, and methyl orange) was carried out by cell suspensions of predominant intestinal anaerobes. . . ."

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  • Corder EH, Buckley CE 3rd, Aspirin, salicylate, sulfite and tartrazine induced bronchoconstriction. Safe doses and case definition in epidemiological studies. J Clin Epidemiol 1995 Oct;48(10):1269-75
    Allergic-like reactions to chemical components of foods and medicines may be common. ... A 15% decrease in the amount of air expired in one second was defined a positive response. ... Doses to which the most sensitive (5%) and practically all (95%) susceptible persons might respectively respond are: metabisulfite 4.6 mg, 255.8 mg; tartrazine 3.4 mg, 885.6 mg; aspirin 0.8 mg, 332.3 mg; and salicylate 2.6 mg, 89.9 mg. Doses within these ranges can be used in epidemiological studies."

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  • Dalal A, Poddar MK. Short-term erythrosine B-induced inhibition of the brain regional serotonergic activity suppresses motor activity (exploratory behavior) of young adult mammals. Pharmacology, Biochemistry, and Behavior, 2009 Jun;92(4):574-82. Epub 2009 Mar 3.
    " Previous studies showed that repeated ingestion of erythrosine B [Red 3] (artificial food color) developed behavioral hyperactivity, but nothing is known about its single administration effect as well as the neurochemical (s) involvement. ... The degree of erythrosine-induced inhibition of both MA [motor activity] and brain regional serotonergic activity was dosage dependent. ... Altogether these results suggest that a single higher dosage of erythrosine (10-200 mg/kg, p.o.) may reduce MA by reducing serotonergic activity with modulation of central dopaminergic activity depending on the brain regions. "

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  • D'Souza SJ, Biggs DF, Aspirin, indomethacin, and tartrazine increase carotid-sinus-nerve activity and arterial blood pressure in guinea pigs. Pharmacology 1987;34(2-3):96-103
    " Acetylsalicylic acid (ASA...), indomethacin (IND...), and tartrazine (TZ...), given intravenously induced dose-dependent increases in carotid-sinus nerve (CSN) activity, accompanied by increases in mean arterial blood pressure . . . These findings indicate that ASA, IND, and TZ act directly on carotid baroreceptors to increase their activity. "

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  • Dees C, Askari M, Garrett S, Gehrs K, Henley D, Ardies CM, Estrogenic and DNA-damaging activity of Red No. 3 in human breast cancer cells. Environ Health Perspect 1997 Apr;105 Suppl 3:625-32
    "Exposure to pesticides, dyes, and pollutants that mimic the growth promoting effects of estrogen may cause breast cancer. ...Red No. 3 increased binding of the ER from MCF-7 cells to the estrogen-responsive element. Consumption of Red No. 3, which has estrogenlike growth stimulatory properties and may be genotoxic, could be a significant risk factor in human breast carcinogenesis."

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  • Dipalma JR, Tartrazine sensitivity, Am Fam Physician 1990 Nov;42(5):1347-50
    "Tartrazine (FD & C Yellow No. 5) is an approved azo dye present in many drugs and food products. ... Tartrazine sensitivity is most frequently manifested by urticaria and asthma... The mechanism of sensitivity is obscure and has been called pseudoallergic. Management consists mainly of avoidance of drugs and food products that contain tartrazine."

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  • EFSA: Revised exposure assessment for Sunset Yellow FCF based on the proposed revised maximum permitted levels of use as a food additive, EFSA Journal 2011;9(9):2349
    " Following a request from the European Commission, the European Food Safety Authority (EFSA) carried out a revised exposure assessment for children of Sunset Yellow FCF (E 110) from its use as a food additive, based on the revised proposed use levels as provided by the European Commission."

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  • Elhkim MO, Héraud F, Bemrah N, Gauchard F, Lorino T, Lambré C, Frémy JM, Poul JM., New considerations regarding the risk assessment on Tartrazine An update toxicological assessment, intolerance reactions and maximum theoretical daily intake in France., Regulatory Toxicology & Pharmacology, 2007 Apr;47(3):308-16. Epub 2007 Jan 10
    "Tartrazine is an artificial azo dye commonly used in human food and pharmaceutical products. Since the last assessment carried out by the JECFA in 1964, many new studies have been conducted, some of which have incriminated tartrazine in food intolerance reactions. The aims of this work are to update the hazard characterization and to revaluate the safety of tartrazine. Our bibliographical review of animal studies confirms the initial hazard assessment conducted by the JECFA, and accordingly the ADI established at 7.5mg/kg bw. From our data, in France, the estimated maximum theoretical intake of tartrazine in children is 37.2% of the ADI at the 97.5th percentile. It may therefore be concluded that from a toxicological point of view, tartrazine does not represent a risk for the consumer. It appears more difficult to show a clear relationship between ingestion of tartrazine and the development of intolerance reactions in patients. These reactions primarily occur in patients who also suffer from recurrent urticaria or asthma. The link between tartrazine consumption and these reactions is often overestimated, and the pathogenic mechanisms remain poorly understood. The prevalence of tartrazine intolerance is estimated to be less than 0.12% in the general population. Generally, the population at risk is aware of the importance of food labelling, with the view of avoiding consumption of tartrazine. However, it has to be mentioned that products such as ice creams, desserts, cakes and fine bakery are often sold loose without any labelling."

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  • el-Saadany SS, Biochemical effect of chocolate colouring and flavouring like substances on thyroid function and protein biosynthesis. Nahrung 1991;35(4):335-43
    "Synthetic chocolate colourant, flavourant and the mixture of both were administered to healthy adult male albino rats to evaluate their effect on the nucleic acids metabolism,... total serum protein, thyroid hormones (T4 and T3) and nuclease enzymes, ... in brain, liver, and kidneys. Also, the activity of the fundamental enzymes ... (G-6-PD and 6-PGD), as well as total lipids and cholesterol contents in the same organs were studied. Ingestion of the studied food additives significantly increased serum protein, RNA and T4 hormone, while, DNA and T3 hormone were insignificantly elevated. In connection with this, the hydrolytic enzymes of nucleic acids... were stimulated by all studied food additives and in all mentioned organs. The activity of G-6-PD and 6-PGD ... increased. The highest increase was noticed in rats fed on diets supplemented with the mixture of both colourant and flavourant followed by colourant then flavourant, respectively."

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  • Ershoff BH., Effects of diet on growth and survival of rats fed toxic levels of tartrazine (FD & C Yellow No. 5) and sunset yellow FCF (FD & C Yellow No. 6). The Journal of nutrition. 1977 May;107(5):822-8
    " Tests were conducted on the effects of diet on the response of immature male rats to massive doses of tartrazine (FD&C Yellow No.5) and Sunset Yellow FCF (FD&C Yellow No. 6). When incorporated at a 5% level in a stock diet, tartrazine and Sunset Yellow FCF had no grossly observable toxic effects. When fed with a purified diet, however, both tartrazine and Sunset Yellow FCF at 5% level in the diet resulted in a marked retardation in growth, an unthrifty appearance of the fur and death of 50% or more of the rats within an experimental period of 14 days. . . . "

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  • EFSA: Scientific Opinion on the re-evaluation Tartrazine (E 102).   
    "The Panel on Food Additives and Nutrient Sources added to Food provides a scientific opinion re-evaluating the safety of Tartrazine (E 102). . . The Panel notes that Tartrazine was negative in long-term carcinogenicity studies and that the effects on nuclear DNA migration observed in the mouse in vivo Comet assay are not expected to result in carcinogenicity. The Panel also concurrs with the conclusion from a previous EFSA opinion on the McCann et al. study that the findings of the study cannot be used as a basis for altering the ADI, and additionally considered that the Tanaka study can also not be used as a basis for altering the ADI. The Panel concludes that the present database does not give reason to revise the ADI of 7.5 mg/kg bw/day. The Panel also concludes that at the maximum reported levels of use, refined intake estimates are below the ADI. The Panel concludes that Tartrazine appears to be able to elicit intolerance reactions in a small fraction of the exposed population.The Panel also notes that sensitive individuals may react to Tartrazine at dose levels within the ADI. "

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  • FDA: FDA Public Health Advisory: Reports of blue discoloration and death in patients receiving enteral feedings tinted with the dye, FD&C Blue No. 1   
    "Dear Health Care Professional:
    The Food and Drug Administration (FDA) would like you to be aware of several reports of toxicity, including death, temporally associated with the use of FD&C Blue No. 1 (Blue 1) in enteral feeding solutions. . . in vitro evidence that Blue 1 can be a mitochondrial toxin lends plausibility to the idea ... "

    See full report by clicking on the title above.

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  • Federal Register: International Trade Commission, Allura Red Coloring from India - determinations
    * US company complained that importing subsidized Red 40 cheaply from India would harm them (the company), but the anti-dumpling conference determined it was okay.

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  • Gallagher JS, Splansky GL, Bernstein IL, Inhibition of platelet aggregation by tartrazine and a pyrazolone analogue in normal and allergic individuals. Clin Allergy 1980 Nov;10(6):683-90
    "The effect of tartrazine (T) (yellow dye No. 5) and one of its metabolites an aminopyrazolone analogue (...SCHP) upon collagen-induced platelet aggregation (C-PA) was investigated ... The mean inhibitory concentrations of SCHP were similar to aspirin in both atopic and normal individuals. ... this in vitro system may be a useful method of assessing non-immune mechanisms involved in reactions to tartrazine."

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  • Yonglin G, Chunmei L, Jingyu S, Huaxian Y, Xiulin A, Haizhu J, Effect of Food Azo Dye Tartrazine on Learning and Memory Functions in Mice and Rats, and the Possible Mechanisms Involved, Journal of Food Science, Volume 76, Issue 6, pages T125–T129, August 2011
    " . . . The present study was conducted to evaluate the toxic effect of tartrazine on the learning and memory functions in mice and rats. . . The results indicated that tartrazine extract significantly enhanced active behavioral response to the open field, increased the escape latency in Morris water maze test, and decreased the retention latency in step-through tests. The decline in the activities of catalase glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) as well as a rise in the level of malonaldehyde (MDA) were observed in the brain of tartrazine-treated rats . . .from oxidative damage. . . "

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  • Granville LA, Finch C., Blue colon at autopsy. Arch Pathol Lab Med. 2001 May;125(5):599.
    Comment on Boutilier 2000, Green colon: an unusual appearance at autopsy.

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  • Hashem MM, Atta AH, Arbid MS, Nada SA, Asaad GF., Immunological studies on Amaranth, Sunset Yellow and Curcumin as food colouring agents in albino rats. Food and Chemical Toxicology, 2010 Jun;48(6):1581-6. Epub 2010 Mar 21.
    " ... This study was carried out to investigate the effect of oral administration of Amaranth [Red 2], Sunset Yellow [Yellow 6] and Curcumin [natural coloring from turmeric] for 4 weeks at doses of 47, 315 and 157.5 mg/kg b. wt. ... Results revealed that oral administration of Amaranth, Sunset Yellow and Curcumin did not affect the body weight gain or the spleen weight. On the other hand Sunset Yellow and Curcumin significantly decreased the weight of thymus gland of the rats. Total leukocyte count were not affected while Amaranth and Curcumin-treated rats revealed a significant decrease in neutrophiles and monocytes and a compensatory increase in lymphocytes. Moreover, oral administration of Sunset Yellow revealed a significant decrease in monocyte percent. Amaranth, Sunset Yellow and Curcumin significantly decreased the delayed hyper sensitivity. Total serum protein, albumin, total globulin and albumin/globulin (A/G) ratio were not affected by administration of the colouring agents. Oral administration of Amaranth increases the density of albumin band. On the other hand oral administration of Curcumin decreases the density of the albumin band. Oral administration of any of the tested colouring agents did not change the density of globulin region as compared to control group. In conclusion we found that both synthetic (Amaranth and Sunset Yellow) and natural (Curcumin) colouring agents used at doses up to 10 times the acceptable daily intake exerted a depressing effect on the cellular but not humoral immune response. "

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  • Hedman SE, Andersson RG, Effects of tartrazine of different contractile stimuli in guinea pig tracheal muscle. Acta Pharmacol Toxicol (Copenh) 1981 Feb;48(2):101-7
    " Tracheal smooth muscle obtained from ovalbumin-sensitized guinea pigs contracted with micromolar concentrations of tartrazine and indomethacin. . . .We suggest that SRS-A plays an important role in the immediate hypersensitivity reactions of tartrazine and indomethacin in guinea pig trachea. "

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  • Huang SW, Borum PR, Study of skin rashes after antibiotic use in young children. Clin Pediatr (Phila) 1998 Oct;37(10):601-7
    After having a rash upon antibiotic use, 62 children were given dye-free antibiotics at the next infection. "... Of the 62 patients who received dye-free suspensions, only eight developed a mild skin rash, which was managed successfully. ..."

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  • Ishihara Y, Kitamura S, Experimental investigation on the pathogenesis of tartrazine-induced asthma. Tohoku Journal of Experimental Medicine 1979 Nov;129(3):303-9.
    "... The contractile responses of guinea pig tracheal tissues induced by various bronchoconstrictors were potentiated in the presence of tartrazine. These results may suggest that tartrazine-induced asthma is not induced by inhibition of PGLS [prostaglandin-like substance] synthesis, but induced by potentiation of bronchoconstrictor responses."

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  • Jabeen HS1, ur Rahman S, Mahmood S, Anwer S., Genotoxicity assessment of amaranth and allura red using Saccharomyces cerevisiae. Bulletin of Environmental Contamination and Toxicology. 2013 Jan;90(1):22-6
    " Amaranth (E123) and Allura red (E129) ... were assessed for their genotoxic potential through comet assay in yeast cells. ... No significant genotoxic activity was observed for Amaranth and Allura red at 28°C but at 37°C direct relation of Amaranth concentration with comet tail was significant and no positive relation was seen with time exposure factor. ... The results indicated that food colors should be carefully used in baking products as heavy concentration of food colors could affect the fermentation process of baking."

    Note: Yes, indeed, one must protect the yeast. How about protecting the people who are going to EAT the items containing these food dyes? Our body temperature is also 37°C ... doesn't that count?

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  • Jones R, Ryan AJ, Wright SE., The Metabolism and Excretion of Tartrazine in Rat, Rabbit and Man. Food & Cosmetics Toxicology. 1964 Oct;2:447-52
    "The excretion and metabolism of tartrazine has been studied in the rat, rabbit and man. The nature of the excretory products depends upon the route of administration. Intra- peritoneal injection leads to the excretion of unchanged colouring. Oral dosage results in the excretion of equivalent amounts of sulphanilic acid which is partly conjugated. A quantitative excretion study has been carried out. The reasons for the resistance of tartrazine to the action of mammalian azo reductase are discussed."

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  • Kamel MM, El-lethey HS, The Potential Health Hazard of Tartrazine and Levels of Hyperactivity, Anxiety-Like Symptoms, Depression and Anti-social behaviour in Rats. Scroll down to #183 Journal of American Science, 2011;7(6)
    " The current research aimed to determine the influence of different doses of exposure to tartrazine on levels of hyperactivity, anxiety, depression and anti-social behaviours in rats. . . Tartrazine-treated rats showed hyperactivity in open field test presented by increased horizontal locomotion. Anxiogenic effect of tartrazine was evidently observed during open field, elevated plus-maze and dark-light transition tests. Furthermore, tartrazine intake significantly promoted depression as expressed by prolonged immobilization during forced swim test. Impairment in social interaction test was also detected signifying the relevance of administered dose especially on numbers of bouts of social contacts. This study provides sufficient scientific evidence that a causal link truly exists between tartrazine and inflection of hyperactivity, anxiety and depression-like behaviours in rats and points to the hazardous impact of tartrazine on public health. "

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  • Koutsogeorgopoulou L, Maravelias C, Methenitou G, Koutselinis A, Immunological aspects of the common food colorants, amaranth and tartrazine. Vet Hum Toxicol 1998 Feb;40(1):1-4
    "We describe ... the cytotoxic and immunosuppressive effects of food colorants such as amaranth [Red #2] and tartrazine [Yellow #5].... The results showed clear immunosuppressive effects from the 2 substances tested, although the concentrations chosen for this study proved to be non-cytotoxic..."

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  • Kumar A, Aitas AT, Hunter AG, Beaman DC, Sweeteners, dyes, and other excipients in vitamin and mineral preparations. Clin Pediatr (Phila) 1996 Sep;35(9):443-50
    "Multivitamins and mineral preparations are widely used for infants and children. All of these preparations contain a variety of excipients ("inert ingredients"). ...The information about sweeteners, dyes, and other excipients (flavorings, preservatives, stabilizers, and fillers) for 41 chewable/liquid multivitamin and mineral preparations was obtained and tabulated. ... The FD&C yellow #6 (sunset yellow) was the most common dye, present in 46% (19/41) of the preparations followed by FD&C Red #40 in 29% (12/41). ... The mandatory listing of all excipients is the only way to assure that physicians and consumers will be fully informed about the hidden ingredients."

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  • Kumar A, Rawlings RD, Beaman DC.. The mystery ingredients: sweeteners, flavorings, dyes, and preservatives in analgesic/antipyretic, antihistamine/decongestant, cough and cold, antidiarrheal, and liquid theophylline preparations. Pediatrics 1993 May;91(5):927-33
    " ...Pharmaceutical preparations may contain a variety of excipients ("inert ingredients"). . . Information about the excipients in a particular preparation is not readily available. . . Information about excipients in 102 chewable and liquid preparations was compiled. An average preparation contained two sweeteners. Saccharin and sucrose were the most common sweeteners found. . . For 36 of the 102 preparations, type of flavoring was not specified. In the remaining preparations, cherry was the most common flavoring, followed by vanilla and lemon. Twenty-one different dyes and coloring agents were used. Red dye No. 40 was the most common (42/102), followed by yellow No. 6 (27/102). Of the eight preservatives used, sodium benzoate and methylparabens were present in 42 and 27 of the preparations, respectively. . . The tables should be helpful to physicians in selecting preparations containing different excipients when an adverse reaction occurs. The mandatory labeling of excipients in all pharmaceutical preparations is the only way that physicians and patients can be fully informed. "

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  • Kumar A, Weatherly MR, Beaman DC. Sweeteners, flavorings, and dyes in antibiotic preparations. Pediatrics 1991 Mar;87(3):352-60
    " Even though a variety of adverse effects caused by sweeteners, flavorings, and dyes in susceptible individuals have been reported, there is no good single reference with information about these substances in pediatric antimicrobials. Data on sweeteners, flavorings, and dyes in 91 antimicrobial preparations were collected. Sucrose was present in 74 (85%) of 87 preparations, followed by saccharin in 30 (34%) preparations. Mannitol, lactose, and sorbitol were each present in 7 preparations. None of the preparations were free of sweeteners. Thirty-four (37%) of 91 preparations did not specify the flavoring content. While cherry was the most common flavoring used, there were 25 other flavorings. Thirteen different dyes and coloring agents were used in these antimicrobials. Red dye no. 40 was present in 45% of preparations. . . . "

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  • Lafferman JA, Silbergeld EK Erythrosin B inhibits dopamine transport in rat caudate synaptosomes., Science. 1979 Jul 27;205(4404):410-2.
    " Erythrosin B is a member of a class of fluorescein dyes that are suggested to elicit hyperkinesis when ingested by susceptible children. We found that erythrosin B inhibits dopamine uptake . . . Erythrosin B also decreased nonsaturable binding of dopamine to the synaptosome membrane. The inhibitory action of erythrosin B on dopamine uptake is consistent with the hypothesis that erythrosin B can act as a central excitatory agent able to induce hyperkinetic behavior. "

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  • Lancaster FE, Lawrence JF, Determination of benzidine in the food colours tartrazine and sunset yellow FCF, by reduction and derivatization followed by high-performance liquid chromatography. Food Addit Contam 1999 Sep;16(9):381-90
    "Free and bound benzidine, a non-sulphonated aromatic amine (NSAA), were determined in the food colours tartrazine and sunset yellow FCF. . . . Levels of total benzidine . .. ranged from < 5 to 270 ng/g. Total aniline was also determined (0.2-188 micrograms/g). . . ."

    NOTE: The Code of Federal Regulations, Title 21, Revised April 1, 2002, specifies that Tartrazine may contain "Benzidine, not more than 1 part per billion." That is 1 ng/g

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  • Lau K, McLean WG, Williams DP, Howard CV., Synergistic Interactions Between Commonly Used Food Additives in a Developmental Neurotoxicity Test. Toxicol Sci. 2006 Mar;90(1):178-87, 2005 Dec 13; [Epub ahead of print]
    " Exposure to non-nutritional food additives during the critical development window has been implicated in the induction and severity of behavioural disorders such as attention deficit hyperactivity disorder (ADHD). . . We therefore examined the neurotoxic effects of four common food additives in combinations of two (Brilliant Blue and L-glutamic acid, Quinoline Yellow and aspartame) to assess potential interactions. . . Neurotoxicity was measured as an inhibition of neurite outgrowth. . . . Theoretical exposure to additives was calculated based on analysis of content in foodstuff, and estimated percentage absorption from the gut. Inhibition of neurite outgrowth was found at concentrations of additives theoretically achievable in plasma by ingestion of a typical snack and drink. . . both combinations had a straightforward additive effect on cytotoxicity. These data have implications for the cellular effects of common chemical entities ingested individually and in combination."

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    Now here's a color we can like:
  • Lechner JF, Wang LS, Rocha CM, Larue B, Henry C, McIntyre CM, Riedl KM, Schwartz SJ, Stoner GD, Drinking water with red beetroot food color antagonizes esophageal carcinogenesis in N-nitrosomethylbenzylamine-treated rats. Journal of Medicinal Food. 2010 Jun;13(3):733-9.
    " This study was undertaken to determine if the oral consumption of red beetroot food color would result in an inhibition of N-nitrosomethylbenzylamine (NMBA)-induced tumors in the rat esophagus. Rats were treated with NMBA and given either regular water ad libitum or water containing 78 microg/mL commercial red beetroot dye, E162. The number of NMBA-induced esophageal papillomas was reduced by 45% (P < .001) in animals that received the food color compared to controls. The treatment also resulted in reduced rates of cell proliferation in both precancerous esophageal lesions and in papillomas of NMBA-treated rats, as measured by immunohistochemical staining of Ki-67 in esophageal tissue specimens. ... Compared to rats treated with NMBA only, the levels of angiogenesis and inflammation in the beetroot color-consuming animals were reduced, and the apoptotic rate was increased. ... Importantly, consumption of the dye in the drinking water for a period of 35 weeks did not appear to induce any overt toxicity. ... "

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  • Lethco EJ, Webb JM., The fate of FD&C blue no. 2 in rats. Journal of Pharmacology & Experimental Therapeutics., 1966 Nov;154(2):384-9.
    " The fate of FD&C blue no. 2 was studied in rats after oral and intravenous administration of material labeled with S35. After intravenous injections, an average of 23% of the radioactivity was excreted in the urine after 30 min and increased until 63% was accounted for after 6 hr. The amount found in the bile accounted for about 10% of the dose with no significant increase after the first 1/2 hour. Isatin-5-sulfonic acid and 5-sulfoanthranilic acid appeared in the urine after 2 hr. After 6 hr, two-thirds of the urinary radioactivity remained as unchanged dye. The results after oral administration of the dye at several levels suggested that it was poorly absorbed from the alimentary tract, with less than 3% of the radioactivity appearing in the urine after 3 days. Column and paper chromatography of the urine indicated that the radioactivity was composed of the unchanged dye and its two oxidative products. The amounts found in the feces were due to unabsorbed dye rather than to biliary excretion. Orally administered 5-sulfoanthranilic acid was absorbed to a greater extent than the dye; an average of 24% appeared in the urine after 2 days. "

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  • Levitan H, Ziylan Z, Smith QR, Takasato Y, Rapoport SI, Brain uptake of a food dye, erythrosin B, prevented by plasma protein binding. Brain Res 1984 Nov 19;322(1):131-4
    "... Thus, significant brain uptake of intravascular dye is normally prevented by its binding to plasma protein (greater than 99% bound) and by the blood-brain barrier impermeability to the dye-protein complex. Sensitivity to food dyes such as erythrosin B in some individuals may reflect altered plasma protein binding capacity, which can vary with age and disease."

    EXPLANATION OF PROTEIN-BINDING:
    Quoted from Drugs and Human Behavior, Second Ed., Palfai & Jankiewicz, 1997 (p.55)

    "Many drugs attach themselves to the large protein globules in the blood, particularly to albumin, the predominant protein. These bound drugs are then trapped in the capillaries unable to act, because the capillary pores, wide as they are, are still smaller than the protein globules. Such a drug is in the position of a person chained to an elephant, trying to climb out a porthole. Ninety percent of the antipsychotic drug chlorpromazine (Thorazine) and 99 percent of the tranquilizer diazepam (Valium) binds with proteins... Bound and unbound portions of a drug in the bloodstream balance in a type of equilibrium ... Different drugs protein-bind to different extents, but the ratio of bound to unbound molecules for a particular drug is a constant. Chlorpromazine ions will always be found in the blood 90 percent bound to 10 percent free. As the free 10 percent diffuses out of circulation, bound molecules free themselves to maintain the proportion. Hence, chlorpromazine escapes from the blood slowly, at a low, steady level, as the body works on the small portion of the drug available at any given moment. ... One method of overcoming the impediments posed by protein-binding ... is to administer an initial dose of the drug large enough to saturate the binding site and then give more to provide a satisfactory effect as well. Another technique is to administer a second drug that exhibits more of an affinity for the tissue than the first. This second drug unseats the molecules of the first drug and replaces them in the tissue [blood]. The first drug is then freed for action. This mechanism can cause poisoning if a drug is accidentally bumped from its binding site, and blood concentrations suddenly soar to toxic levels."

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  • Levitan H. Food, drug, and cosmetic dyes: Biological effects related to lipid solubility. (1977).Proceedings of the National Academy of Sciences, U.S.A., 74, 2914-2918.
    "The synthetic coloring agents increased the resting membrane potential and conductance of the neurons in a dose-dependent manner by increasing the potassium permeability of the membrane relative to that of other ions."

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  • Logan WJ, Swanson JM (1979) Erythrosin B Inhibition of Neurotransmitter Accumulation by Rat Brain Homogenate., Science, 206, 363-364.
    "A mixture of seven food dyes inhibited the accumulation of eight neurotransmitters or neurotransmitter precursors by rat brain homogenate."

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  • Lowry MD, Hudson CF, Callen JP, Leukocytoclastic vasculitis caused by drug additives. J Am Acad Dermatol 1994 May;30(5 Pt 2):854-5
    "Chronic cutaneous small vessel (leukocytoclastic) vasculitis (LCV) is a process believed to be related to the presence of circulating immune complexes. ... We report a patient with chronic cutaneous LCV in whom the presumed cause was an excipient (a dye) used in the capsule form of lithium carbonate. Furthermore, ingestion of foods containing dyes results in a disease flare in our patient."

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  • Lucarelli MR, Shirk MB, Julian MW, Crouser ED., Toxicity of Food Drug and Cosmetic Blue No. 1 dye in critically ill patients. Chest. 2004 Feb;125(2):793-5.
    " Food Drug and Cosmetic Blue No. 1 dye (FD&C Blue No. 1) is commonly added to enteral nutrition formulations in order to facilitate the detection of gastric aspirate in tracheal secretions of critically ill patients. However, reports of systemic blue dye absorption and associated adverse outcomes are emerging. We report two cases of abnormal systemic absorption of FD&C Blue No. 1 in critically ill patients who subsequently died of refractory shock and metabolic acidosis. Risk factors and mechanisms of FD&C Blue No. 1 toxicity are discussed, and alternate approaches to gastric aspiration detection in critically ill patients are considered."

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  • Maloney JP, Halbower AC, Fouty BF, Fagan KA, Balasubramaniam V, Pike AW, Fennessey PV, Moss M, Systemic Absorption of Food Dye in Patients with Sepsis N Engl J Med 2000 Oct 5;343(14):1047-8
    " Autopsies of both patients revealed green or blue discoloration of the skin and internal organs, without gastrointestinal perforation. . . it is unlikely that oral-intake limits established by the Food and Drug Administration (FDA) for blue dye no. 1 (12 mg per kilogram of body weight per day) were exceeded. . . . FD&C blue dye no. 1 was approved by the FDA for use in food . . . However, these experiments were performed in healthy animals. . . . Blue dye no. 1, . . . reduces oxygen consumption by a factor of eight in mitochondrial preparations in vitro. . . . Although both patients had serious underlying illnesses, their condition was improving before they received the dye and turned color. . . .We encourage judicious use of this food dye in patients with sepsis or other illnesses associated with increased gastrointestinal permeability. "

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  • Mehedi N, Ainad-Tabet S, Mokrane N, Addou S, Zaoui C, Kheroua O, Saidi D., Reproductive Toxicology of Tartrazine (FD and C Yellow No. 5) in Swiss Albino Mice. American Journal of Pharmacology and Toxicology 4 (4): 128-133, 2009
    " ... The current study evaluated the effect of sub-chronic consumption of tartrazine on the male reproductive system. Results: ... sperm count was decreased and sperm abnormalities were increased in the 2.5% tartrazine treated groups compared to the control. Sperm motility and histological changes in testis were observed in the middle and high treated groups.

    Conclusion/Recommendations: We concluded that excessive tartrazine consumption can have adverse effects on the male reproductive function. We suggested conducting surveys among the population to estimate their daily intake."

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  • Mizutani T., Toxicity of Xanthene Food Dyes by Inhibition of Human Drug-Metabolizing Enzymes in a Noncompetitive Manner., J Environ Public Health. 2009;2009:953952. Epub 2009 Aug 23.
    " The synthetic food dyes studied were rose bengal (RB), phroxine (PL), amaranth, erythrosine B (ET), allura red, new coccine, acid red (AR), tartrazine, sunset yellow FCF, brilliant blue FCF, and indigo carmine. . . We showed the inhibitory effect of xanthene dye on human UGT1A6 [enzyme] activity. . . Human CYP3A4 [enzyme] and P-glycoprotein were also inhibited by basic xanthene food dyes. . . . This result suggests that superoxide anions, originating on dyes by light irradiation, must attack drug-metabolizing enzymes. It is possible that red cosmetics containing phloxine, erythrosine, or rose bengal react with proteins on skin under lighting and may lead to rough skin. "

    Discussion section: " ...these dyes should not influence drug metabolism . . . under normal conditions in the body; however, it is necessary for some patients with ulcers in the gut to avoid the ingestion of chemical food dyes. It is also possible that some cosmetics contain red xanthene dyes, activated by light irradiation, which may injure and lead to rough skin. Thus, it is recommended for a person with facial inflammation to avoid cosmetics."

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  • MMWR / CDC: Lead poisoning associated with imported candy and powdered food coloring--California and Michigan. MMWR Morb Mortal Wkly Rep. 1998 Dec 11;47(48):1041-3.
    " Although the most common source of pediatric lead poisoning is dust within the home that contains deteriorated lead-based paint from walls and windowsills, other less common sources (1-3) can result in excess exposure among children . . . This report describes two cases of pediatric lead poisoning associated with eating imported candy and food stuffs and underscores the importance of thorough history-taking to identify unusual sources of lead exposure. "

    We wonder why this does not underscore the importance of getting the lead out of artificial food colorings?

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  • Moutinho IL, Bertges LC, Assis RV., Prolonged use of the food dye tartrazine (FD&C yellow no 5) and its effects on the gastric mucosa of Wistar rats. Brazilian Journal of Biology, 2007 Feb;67(1):141-5.
    " ... The treatment group received 7.5 mg x kg(-1) x day(-1) of tartrazine daily in drinking water offered ad libitum for ten months from weaning to the age of twelve months. There was a significant increase in the number of lymphocytes and eosinophils of the gastric antrum mucosa. No carcinogenetic changes in any gastric area were observed during the study. As tartrazine belongs to the azo class, it is still a possible food carcinogen. Other studies with different doses and schedules, observing their effects associated to other carcinogens should be carried out if their safe use is to be recommended. "

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  • Mpountoukas P, Pantazaki A, Kostareli E, Christodoulou P, Kareli D, Poliliou S, Mourelatos C, Lambropoulou V, Lialiaris T. Cytogenetic evaluation and DNA interaction studies of the food colorants amaranth, erythrosine and tartrazine. Food and Chemistry Toxicology,2010 Oct;48(10):2934-44. Epub 2010 Jul 25.
    " Food coloring agents, amaranth [Red 2], erythrosine [Red 3] and tartrazine [Yellow 5] have been tested at 0.02-8mM in human peripheral blood cells in vitro, in order to investigate their genotoxic, cytotoxic and cytostatic potential. ... Additionally DNA electrophoretic mobility experiments showed that these colorants are obviously capable for strong binding to linear dsDNA causing its degradation. ... Our results indicate that these food colorants had a toxic potential to human lymphocytes in vitro and it seems that they bind directly to DNA."

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  • APA: Inactive ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics Committee on Drugs. Pediatrics 1997 Feb;99(2):268-78
    "Because of an increasing number of reports of adverse reactions associated with pharmaceutical excipients, in 1985 the Committee on Drugs issued a position statement recommending that the Food and Drug Administration mandate labeling of over-the-counter and prescription formulations to include a qualitative list of inactive ingredients. However, labeling of inactive ingredients remains voluntary. ... The original statement, therefore, has been updated and its information expanded.

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  • Peng W, Cotrina ML, Han X, Yu H, Bekar L, Blum L, Takano T, Tian GF, Goldman SA, Nedergaard M., Systemic administration of an antagonist of the ATP-sensitive receptor P2X7 improves recovery after spinal cord injury.
    Proc Natl Acad Sci U S A. 2009 Jul 28;106(30):12489-93. Epub 2009 Jul 27.
    " Traumatic spinal cord injury is characterized by an immediate, irreversible loss of tissue at the lesion site, as well as a secondary expansion of tissue damage over time. Although secondary injury should, in principle, be preventable, no effective treatment options currently exist for patients with acute spinal cord injury (SCI). ...Administration of BBG 15 min after injury reduced spinal cord anatomic damage and improved motor recovery without evident toxicity. Moreover, BBG treatment directly reduced local activation of astrocytes and microglia, as well as neutrophil infiltration. These observations suggest that BBG not only protected spinal cord neurons from purinergic excitotoxicity, but also reduced local inflammatory responses. Importantly, BBG is a derivative of a commonly used blue food color (FD&C blue No. 1), which crosses the blood-brain barrier. Systemic administration of BBG may thus comprise a readily feasible approach by which to treat traumatic SCI in humans."

    (In case you were wondering why we consider artificial food dyes similar to drugs.)

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  • Piruzian LA, Kovalev IE, Kovaleva VL., Dyes with properties of modulators of redox processes as potential immunotropic agents
    Izv Akad Nauk Ser Biol. 2001 Sep-Oct;(5):563-72.
    " We performed an analysis of the biological activity of dyes possessing certain redox potential. This provided a theoretical basis for the development of a new trend in pharmacology. We demonstrate the wide potential associated with the use of this group of substances to regulate various biochemical processes in the immunity system."

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  • Poul M, Jarry G, Elhkim MO, Poul JM., Lack of genotoxic effect of food dyes amaranth, sunset yellow and tartrazine and their metabolites in the gut micronucleus assay in mice.
    Food and Chemoca; Toxicology 2009 Feb;47(2):443-8. Epub 2008 Dec 6
    " The food dyes amaranth, sunset yellow and tartrazine were administered twice, at 24h intervals, by oral gavage to mice and assessed in the in vivo gut micronucleus test for genotoxic effects ... and toxicity ... Parent dye compounds and their main aromatic amine metabolites were detected in significant amounts in the environment of colonic cells. Acute oral exposure to food dye additives amaranth, sunset yellow and tartrazine did not induce genotoxic effect in the micronucleus gut assay in mice at doses up to 2000 mg/kg b.w. Food dyes administration increased the mitotic cells at all dose levels when compared to controls. These results suggest that the transient DNA damages previously observed in the colon of mice treated by amaranth and tartrazine by the in vivo comet assay [Sasaki, Y.F., Kawaguchi, S., Kamaya, A., Ohshita, M., Kabasawa, K., Iwama, K., Taniguchi, K., Tsuda, S., 2002. The comet assay with 8 mouse organs: results with 39 currently used food additives. Mutat. Res. 519, 103-119] are unable to be fixed in stable genotoxic lesions and might be partly explained by local cytotoxicity of the dyes."

    Note: It may be "lack of genotoxic effect" but certainly not lack of toxic effect ... too bad they didn't say it like that - ed.

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  • Prival MJ, Peiperl MD, Bell SJ, Determination of combined benzidine in FD & C yellow no. 5 (tartrazine), using a highly sensitive analytical method.
    Food and Chemical Toxicology 1993 Oct;31(10):751-8
    " 53 samples of FD & C Yellow No. 5 (tartrazine; Colour Index No. 19140) were examined for combined benzidine. . . . The limit of quantitation for benzidine in FD & C Yellow No. 5 by this method is 5 ng/g. 25 samples of FD & C Yellow No. 5 were found to contain 7-83 ng/g of combined benzidine that was released by dithionite reduction. . . ."

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  • Rao KV, Fernandes CL, Progressive effects of malachite green at varying concentrations on the development of N-nitrosodiethylamine induced hepatic preneoplastic lesions in rats. Tumori 1996 May-Jun;82(3):280-6
    "Malachite green (MG) is a triarylmethane textile dye which is banned for use as a food colour. However, despite the ban it is used unscrupulously as a food colouring agent. It is also used extensively for dyeing silk, wool, jute, leather, cotton and also as a laboratory reagent,... MG tested at all the three concentrations and PB were found to enhance liver carcinogenesis to a significant extent ..."

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  • Reyes FG, Valim MF, Vercesi AE. Effect of organic synthetic food colours on mitochondrial respiration. Food Additives and Contaminants. 1996 Jan;13(1):5-11
    " ... The compounds tested were: Erythrosine, Ponceau 4R, Allura Red, Sunset yellow, Tartrazine, Amaranth, Brilliant Blue, Blue, Fast Red E, Orange GGN and Scarlet GN. All food colours tested inhibited mitochondrial respiration ...This inhibition varied largely, e.g. from 100% to 16% for Erythrosine and Tartrazine respectively, ...This effect was dose related ...."

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  • Rosenkranz HS, Klopman G. Structural basis of the mutagenicity of 1-amino-2-naphthol-based azo dyes. Mutagenesis 1990 Mar;5(2):137-46
    " A structure-activity study of 1-amino-2-naphthol derived azo dyes using CASE, the Computer Automated Structure Evaluation system, revealed that for optimal mutagenicity, reduction of the azo bond was required. . .it has long been known that sulfonation of azo dyes resulted in decreased carcinogenicity . . . Unexpectedly, CASE indicates that one of the aromatic amines obtained upon azo reduction of FD and C Red no. 40 is predicted to be mutagenic (making mutations or changes in DNA)"

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  • Sasaki YF, Kawaguchi S, Kamaya A, Ohshita M, Kabasawa K, Iwama K, Taniguchi K, Tsuda S., The comet assay with 8 mouse organs: results with 39 currently used food additives. Mutation Research 2002 Aug 26;519(1-2):103-19
    We determined the genotoxicity of 39 chemicals currently in use as food additives. . . Of all the additives, dyes were the most genotoxic. Amaranth, Allura Red, New Coccine, Tartrazine, Erythrosine, Phloxine, and Rose Bengal induced dose-related DNA damage in the glandular stomach, colon, and/or urinary bladder. All seven dyes induced DNA damage in the gastrointestinal organs at a low dose (10 or 100mg/kg). Among them, Amaranth, Allura Red, New Coccine, and Tartrazine induced DNA damage in the colon at close to the acceptable daily intakes (ADIs). Two antioxidants (butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT)), three fungicides (biphenyl, sodium o-phenylphenol, and thiabendazole), and four sweeteners (sodium cyclamate, saccharin, sodium saccharin, and sucralose) also induced DNA damage in gastrointestinal organs. Based on these results, we believe that more extensive assessment of food additives in current use is warranted.

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  • Shimada C, Kano K, Sasaki YF, Sato I, Tsudua S, Differential colon DNA damage induced by azo food additives between rats and mice. Journal of Toxicological Sciences 2010;35(4):547-54.
    " Azo dyes, amaranth, allura red and new coccine, which are currently used as food color additives in Japan, have been reported to cause colon specific DNA damage in mice. To examine species difference in the DNA damage between rats and mice, each of dyes was administered to male mice (1 and 10 mg/kg) and male rats (10, 100 and 1,000 mg/kg) by gavage. Brain, lung, liver, kidney, glandular stomach, colon, urinary bladder and bone marrow were sampled 3 hr (for mice) and 3, 6, 12 and 24 hr (for rats) after the treatment. The alkaline comet assay showed DNA damage in the mouse colon 3 hr after the administration of all of the dyes at 10 mg/kg. In rats, however, none of the dyes damaged DNA. Azo dyes should undergo metabolic reduction in the colon to be adducted to DNA. To determine transit time of the dyes to the colon after their administration, gastric emptying and intestinal transport in mice and rats were examined using brilliant blue FCF (BB) as an indicator. The half times of gastric emptying were 70 and 80 min for mice and rats, respectively; and about 60% of the BB was removed from the stomach 1 hr after the gastric intubation in both mice and rats. BB reached the mouse and rat colon 1 and 3 hr after the administration, respectively. Considering the wide dose range and sampling times well covering the transit time to the colon, rats may be insensitive to these azo dye-induced DNA damage."

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  • Smith PA, Dombro KR, Zidichouski J. Effect of erythrosin B (FD&C Red 3) on hyperpolarizing responses to catecholamines in amphibian sympathetic ganglia. J Pharmacol Exp Ther. 1984 Jul;230(1):221-7.
    " . . . .Xanthine dyes such as erythrosin B have also been reported to inhibit Na-K-adenosine triphosphatase. In agreement with this possibility we found that erythrosin B promoted irreversible inhibition of the (nicotinic) acetylcholine after-hyperpolarization. This response is generated by the electrogenic activity of the Na+ pump. . . The irreversible antagonism of epinephrine and dopamine by erythrosin was specific in that hyperpolarizing responses to muscarinic antagonists such as methacholine were relatively insensitive to the dye. It is therefore concluded that erythrosin B selectively antagonizes responses to catecholamines in amphibian sympathetic ganglia..."

    This study is important as it demonstrates an irreversible effect of food dyes in body cells.

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  • Sobotka TJ, Brodie RE, Spaid SL, Tartrazine and the developing nervous system of rats. Journal of Toxicology and Environmental Health 1977 May;2(5):1211-20.
    "Rat dams were exposed to the artificial food color tartrazine (FD&C Yellow no. 5) at dietary levels of 0, 1, and 2% during gestation and lactation. The experimental offspring were continued on the same diets for approximately 3 months after weaning. No adverse physical or behavioral effects were noted in the dams. Fetal development and postnatal viability of the offspring were also normal. The only effect on postnatal development of the central nervous system (CNS) was a small transient change in neuromotor clinging ability of female offspring. The limited effect of tartrazine on the CNS was further evidenced by the facts that (1) the neurobehavioral profiles of the experimental weanlings revealed no significant abnormalities, and (2) morphochemical analysis of brain tissue, as well as brain weights, revealed no abnormalities. Tartrazine did appear to exert more general signs of toxicity in the offspring--namely, depressed body weight, an apparent reduction in thymus weight, and a slight elevation of red blood cells and hemoglobin."

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  • Sweeney EA, Chipman JK, Forsythe SJ, Evidence for direct-acting oxidative genotoxicity by reduction products of azo dyes. Environ Health Perspect 1994 Oct;102 Suppl 6:119-22
    "...The ingestion of azo dyes has been proposed as one source of potential genotoxic agents. Many intestinal bacteria are able to reduce the azo bond (termed azofission), which liberates the substituted naphthol compounds. ... The superoxide free radical was produced by the azo dyes only after reduction by the intestinal bacteria Enterococcus faecalis and Bacteroides thetaiotaomicron."

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  • Tanaka T. Effects of amaranth on F1 generation mice. Toxicology letters 1992 May;60(3):315-24
    " The color additive, amaranth, (Red No. 2) was given in the diet to provide dietary levels of 0 (control), 0.03, 0.09 and 0.27%, from 5 weeks of age in F0 generation mice to 9 weeks of age in F1 generation mice. . . There was no effect on the parameters of litters, litter size, pup weight and litter weight. The body weight of pups during the lactation period in the treatment groups increased less significantly, and the survival index at postnatal day (PND) 21 of the amaranth 0.27% group was reduced. Developmental parameters, direction of swimming on PND 4 in male pups and olfactory orientation in each sex were significantly reduced in the treatment groups. The dose levels of amaranth in this study influenced some reproductive, developmental and behavioral parameters in mice. "

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  • Tanaka T., Reproductive and neurobehavioral effects of amaranth administered to mice in drinking water. Toxicology and industrial health. 1993 Nov-Dec;9(6):1027-35
    " The color additive amaranth [Red #2] was given in the drinking water at levels of 0 (control), 0.025, 0.075, and 0.225% from 5 weeks of age in F0 generation until F1 generation mice were weaned,. . . Average body weight in both sexes of the F1 mice was significantly increased in the 0.025% group in both sexes. Survival index at postnatal day (PND) 21 was reduced in the 0.025% amaranth group. For the neurobehavioral parameters, surface righting at PND 4 in female offspring and olfactory orientation in both sexes were significantly affected by treatment. Several parameters of movement activity of male offspring at 3 weeks of age were affected in amaranth 0.075% group . . . "

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  • Tanaka T., Reproductive and neurobehavioral effects of Sunset yellow FCF administered to mice in the diet. Toxicol Ind Health 1996 Jan-Feb;12(1):69-79
    Selected reproductive and neurobehavioral parameters were measured in mice given the color additive Sunset Yellow [FD&C Yellow #6] FCF in the diet. The additive was given at levels of 0 (control), 0.15, 0.30, and 0.60%, from five weeks of age in the F0 generation to nine weeks of age in the F1 generation. There were few adverse effects on litter size, weight, or sex ratio. Average body weight . . . was significantly increased . . . In the neurobehavioral parameters, swimming direction was significantly affected in a dose-related manner in male and female offspring . . . Also in the early lactation period, surface righting and negative geotaxis were significantly affected in male offspring in the middle-dose group, and swimming head angle was significantly affected in female offspring in a dose-related manner. The dose levels of Sunset Yellow FCF in this study did produce some adverse effects in reproductive and neurobehavioral parameters.

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  • Tanaka T. Reproductive and neurobehavioural toxicity study of erythrosine administered to mice in the diet. Food Chem Toxicol 2001 May;39(5):447-54
    " Erythrosine was given in the diet to provide levels of 0 (control), 0.005, 0.015 and 0.045% from 5 weeks of age of the F(0) generation to 9 weeks of age of the F(1) generation in mice, and selected reproductive and neurobehavioural parameters were measured. . . .In movement activity of exploratory behaviour, several parameters were significantly changed in the high-dose group, and those effects were dose related in adult females in the F(0) and F(1) generations and in male offspring in the F(1) generation. . . . "

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  • Tanaka T., Reproductive and neurobehavioural toxicity study of tartrazine administered to mice in the diet. Food Chem Toxicol. 2005 Aug 5 (epub ahead of print)
    " Tartrazine was given in the diet . . . and selected reproductive and neurobehavioural parameters were measured. In movement activity of exploratory behaviour in the F(0) generation, number of vertical activity was significantly increased ...The average body weight . . .was significantly increased . . . In behavioural developmental parameters, surface righting . . . was significantly accelerated . . . Cliff avoidance at PND 7 was significantly accelerated . . . Negative geotaxis at PND 4 was significantly delayed . . . number of movement showed a significant tendency to be affected . . . Nevertheless, . . . the actual dietary intake of tartrazine is presumed to be much lower. It would therefore appear that the levels of actual dietary intake of tartrazine is unlikely to produce any adverse effects in humans. "

    Please click on the link to the entire abstract and read it carefully. It is astonishing that in the face of these clear adverse effects on mice, he would conclude that it is not a problem for humans. And his basis for such a conclusion? Simply that we would theoretically eat less than the mice did.

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  • Taylor SL, Dormedy ES. Flavorings and colorings. Allergy 1998;53(46 Suppl):80-2
    " Food Allergy Research and Resource Program, University of Nebraska, Lincoln 68583-0919, USA."

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  • Tsuda S, Murakami M, Matsusaka N, Kano K, Taniguchi K, Sasaki YF. DNA damage induced by red food dyes orally administered to pregnant and male mice. Toxicol Sci 2001 May;61(1):92-9
    " We determined the genotoxicity of synthetic red tar dyes (amaranth (food red No. 2), allura red (food red No. 40), or acid red (food red No. 106), new coccine (food red No. 18). currently used as food color additives in many countries, including JAPAN: ...The assay was positive in the colon 3 h after the administration of amaranth and allura red and weakly positive in the lung 6 h after the administration of amaranth. Acid red did not induce DNA damage in any sample at any sampling time. ...The 3 dyes induced DNA damage in the colon starting at 10 mg/kg. ... 6.5 mg/10 ml of new coccine, induced DNA damage in colon, glandular stomach, and bladder. . . Because the 3 azo additives we examined induced colon DNA damage at a very low dose, more extensive assessment of azo additives is warranted. "

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  • Vorhees CV, Butcher RE, Brunner RL, Wootten V, Sobotka TJ. Developmental toxicity and psychotoxicity of FD and C red dye No. 40 (allura red AC) in rats. Toxicology 1983;28(3):207-17
    " Adult Sprague-Dawley rats were fed diets containing FD and C red dye No. 40 for 2 weeks and were then bred. The diets were continued for the females throughout gestation and lactation and were provided continuously to their offspring thereafter. T. . . Red-40 significantly reduced reproductive success, parental and offspring weight, brain weight, survival, and female vaginal patency development. Behaviorally, R40 produced substantially decreased running wheel activity, and slightly increased postweaning open-field rearing activity. Overall, R40 produced evidence of both physical and behavioral toxicity in developing rats at doses of up to 10% of the diet. (high doses) "

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  • WHO: Evaluation of certain food additives. Fifty-first report of the Joint FAO/WHO Expert Committee on Food Additives. World Health Organ Tech Rep Ser 2000;891:i-viii, 1-168
    " This report presents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, with a view to recommending Acceptable Daily Intakes (ADIs) for humans, and to prepare specifications for the identity and purity of food additives. . . . A summary follows of the Committee's evaluations of toxicological data on specific food additives, . . .The Committee also evaluated the safety of various groups of flavouring agents and assessed the intake of specific food additives, including benzoates, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sulfites and tert-butylhydroquinone (TBHQ). Annexed to the report are tables summarizing the Committee's recommendations for ADIs of the food additives considered, changes in the status of specifications for these substances and specific flavouring agents, and further toxicological studies and other information required or desired. "

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  • Wuthrich B, Adverse reactions to food additives. Ann Allergy 1993 Oct;71(4):379-84
    " Food additives can induce a wide range of adverse reactions in sensitive individuals. ... Two typical cases of a "restaurant syndrome" due to sulfite allergy or sensitivity are described, as well as a case of disulfite-induced urticaria-vasculitis and a case of anaphylactoid purpura associated with tartrazine and benzoates."

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  • Zillich AJ, Kuhn RJ, Petersen TJ, Skin discoloration with blue food coloring.    Ann Pharmacother 2000 Jul-Aug;34(7-8):868-70
    " . . . Twelve hours after the start of enteral nutrition, the patient appeared cyanotic . . . The pediatric code response team was called. Enteral nutrition was stopped and then restarted without blue food coloring. . . . blue food coloring is used with enteral nutrition for detecting aspiration of stomach contents. . . Nurses place an unstandardized amount of blue food coloring into each enteral nutrition bag. . . . No toxicity studies exist for acute or human ingestion, but the National Academy of Sciences lists 363 mg/d of FD&C Blue No. 1 as a safe level for humans. We estimated this child ingested 780-3,940 mg of dye over a 12-hour period. CONCLUSIONS: This is the first known report of an adverse effect from blue food coloring. To prevent similar occurrences within our institution, the blue food coloring for tube feedings will be dispensed by the pharmacy department in standardized units."

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