Comparison of in vitro Toxicities of 8-Prenylnaringenin, Tartrazine and 17ß-Estradiol, Representatives of Natural and Synthetic Estrogens, in Rat and Human Hepatoma Cell Lines.

BACKGROUND: Phytoestrogens have been praised for their beneficial health effects, whereas synthetic xenoestrogens have been connected to ailments. AIMS: To ascertain whether the toxicities of natural and synthetic estrogens differ, we examined the potent phytoestrogen 8-prenylnaringenin (8-PN), the common synthetic xenoestrogen tartrazine, and the physiological estrogen 17ß-estradiol (E2). METHODS: These three compounds were tested for cytotoxicity, cell proliferation and genotoxicity in human HepG2 and rat H4IIE hepatoma cells. RESULTS: All three estrogens elicited cytotoxicity at high concentrations in both cell lines. They also inhibited cell proliferation, with E2 being the most effective. They all tended to increase micronuclei formation. CONCLUSION: Natural estrogens were no less toxic than a synthetic one.

Assessing the Impact of Chemical Algae Management Strategies on Anurans and Aquatic Communities.

Pond management with chemical and biological agents that reduce overgrowth of algae is an important means of maintaining water quality in residential ponds, yet the effects on nontarget species are not fully understood. We assessed the impact of Aquashade (a common nontoxic pond dye) and copper sulfate (a toxic algaecide) on American toad (Anaxyrus americanus), northern leopard frog (Lithobates pipiens), and Cope's gray treefrog (Hyla chrysoscelis) metamorphosis in outdoor mesocosm experiments. We also evaluated the relative impact of tadpole grazing versus chemical treatment on phytoplankton and periphyton abundance. We found no significant effects of pond management treatment on anuran metamorphosis, suggesting that addition of Aquashade and copper sulfate at tested concentrations does not significantly impact anurans under these experimental conditions. Interestingly, we found that the presence of tadpoles more strongly reduced algal abundance than Aquashade or copper sulfate by significantly decreasing phytoplankton and periphyton abundance over time. The present study suggests that anuran tadpoles may be effective at maintaining water quality, and that Aquashade and copper sulfate may have minimal effects on amphibian metamorphosis. Environ Toxicol Chem 2023;42:213-224. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Oral administration of tartrazine (E102) accelerates the incidence and the development of 7,12-dimethylbenz(a) anthracene (DMBA)-induced breast cancer in rats.

BACKGROUND: Despite the considerable advances made in the treatment of cancer, it remains a global threat. Tartrazine (E102) is a synthetic dye widely used in food industries; it has recently been shown to induce oxidative stress (a well known risk factor of cancer) in rat tissues. The present work therefore aimed to assess the impact of a regular consumption of tartrazine on the incidence of breast cancer in rats. METHODS: Forty (40) Wistar rats aged 55 to 60 days were randomly assigned into 5 groups (n = 8) including two groups serving as normal controls and receiving distilled water (NOR) or tartrazine (NOR + TARZ). The three remaining groups were exposed to the carcinogen DMBA (50 mg/kg) and treated for 20 weeks with either distilled water (DMBA), tartrazine 50 mg/kg (DMBA + TARZ) or a natural dye (DMBA + COL). The parameters evaluated were the incidence, morphology and some biomarkers (CA 15-3, estradiol and α-fetoprotein) of breast cancer. The oxidative status and histomorphology of the tumors were also assessed. RESULTS: A regular intake of tartrazine led to an early incidence of tumors (100% in rats that received TARZ only vs 80% in rats that received DMBA only), with significantly larger tumors (p < 0.001) (mass = 3500 mg/kg and volume = 4 cm3). The invasive breast carcinoma observed on the histological sections of the animals of the DMBA + TARZ group was more developed than those of the DMBA group. The increase in serum α-fetoprotein (p < 0.05) and CA 15-3 (p < 0.01) levels corroborate the changes observed in tumors. The presence of oxidative activity in animals of the DMBA + TARZ group was confirmed by a significant decrease (p < 0.001) in the activity of antioxidant enzymes (SOD and catalase) as well as the level of GSH and increase in the level of MDA compared to the rats of the DMBA and NOR groups. CONCLUSION: Tartrazine therefore appears to be a promoter of DMBA-induced breast tumorigenesis in rats through its oxidative potential. This work encourages further studies on the mechanisms of action of tartrazine (E102) and its limits of use.

Unveiling the stimulatory effects of tartrazine on human and bovine serum albumin fibrillogenesis: Spectroscopic and microscopic study.

Amyloid fibrils are playing key role in the pathogenesis of various neurodegenerative diseases. Generally anionic molecules are known to induce amyloid fibril in several proteins. In this work, we have studied the effect of anionic food additive dye i.e., tartrazine (TZ) on the amyloid fibril formation of human serum albumins (HSA) and bovine serum albumin (BSA) at pHs7.4 and 3.5. We have employed various biophysical methods like, turbidity measurements, Rayleigh Light Scattering (RLS), Dynamic Light Scattering (DLS), intrinsic fluorescence, Congo red assay, far-UV CD, transmission electron microscopy (TEM) and atomic force microscopy (AFM) to decipher the mechanism of TZ-induce amyloid fibril formation in both the serum albumins at pHs7.4 and 3.5. The obtained results suggest that both the albumins forms amyloid-like aggregates in the presence of 1.0 to 15.0mM of TZ at pH3.5, but no amyloid fibril were seen at pH7.4. The possible cause of TZ-induced amyloid fibril formation is electrostatic and hydrophobic interaction because sulfate group of TZ may have interacted electrostatically with positively charged amino acids of the albumins at pH3.5 and increased protein-protein and protein-TZ interactions leading to amyloid fibril formation. The TEM, RLS and DLS results are suggesting that BSA forms bigger size amyloids compared to HSA, may be due to high surface hydrophobicity of BSA.

The protective role of crocin in tartrazine induced nephrotoxicity in Wistar rats.

The present study was conducted to investigate the changes in rat kidney tissues after administration of tartrazine (T) and crocine (Cr). The latter was applied for its protective properties. The present study was conducted with the approval of Inonu University, Faculty of Medicine, Experimental Animals Ethics Committee. Forty rats were randomly divided into 4 equal groups (Control, T, Cr, T + Cr). At the end of the experiment, the rats were decapitated. Biochemical and histopathological studies were conducted on excised rat kidney tissues. It was determined that there was a significant increase in MDA, TOS, SOD, CAT, Bun, Creatinine levels in tartrazine administered rat kidney tissues for 21 days, while GSH and TAS levels decreased (P ≤ 0.05) when compared to all other groups. On the other hand, it was identified that Cr administration statistically significantly increased GSH and TAS levels in rat kidney tissues when compared to all other groups and decreased MDA and TOS levels to control group levels (P < 0.05). T group kidney sections exhibited different degrees of collapse in the glomeruli. In most sections, different levels of inflammatory cell infiltration and vascular and capillary congestion were detected in peritubular interstitial tissue. It was determined that T leads to adverse effects on rat kidney tissues. Administration of Cr + T prevented T induced nephrotoxicity. Thus, it was concluded that Cr could be utilized as a new type of anti-tartrazine toxicity agent.

Lack of genotoxicity in vivo for food color additive Tartrazine.

Tartrazine is approved as a food color additive internationally with INS number 102, in the United States as food color subject to batch certification "Food, Drug, and Cosmetic" (FD&C) Yellow No. 5, and in Europe as food color additive with E number 102. In their evaluation of the color (2013), the European Food Safety Authority (EFSA) expressed concerns of potential genotoxicity, based primarily on one genotoxicity study that was not conducted according to Guidelines. The present in vivo genotoxicity study was conducted according to OECD Guidelines in response to EFSA's request for additional data. The animal species and strain, and the tissues examined were selected specifically to address the previously reported findings. The results of this study show clear absence of genotoxic activity for Tartrazine, in the bone marrow micronucleus assay and the Comet assay in the liver, stomach, and colon. These data addressed EFSA's concerns for genotoxicity. The Joint WHO/FAO Committee on Food Additives (JECFA) (2016) also reviewed these data and concluded that there is no genotoxicity concern for Tartrazine. Negative findings in parallel genotoxicity studies on Allura Red AC and Ponceau 4R (published separately) are consistent with lack of genotoxicity for azo dyes used as food colors.

Binding and Inhibitory Effect of the Dyes Amaranth and Tartrazine on Amyloid Fibrillation in Lysozyme.

Interaction of two food colorant dyes, amaranth and tartrazine, with lysozyme was studied employing multiple biophysical techniques. The dyes exhibited hypochromic changes in the presence of lysozyme. The intrinsic fluorescence of lysozyme was quenched by both dyes; amaranth was a more efficient quencher than tartrazine. The equilibrium constant of amaranth was higher than that of tartarzine. From FRET analysis, the binding distances for amaranth and tartrazine were calculated to be 4.51 and 3.93 nm, respectively. The binding was found to be dominated by non-polyelectrolytic forces. Both dyes induced alterations in the microenvironment surrounding the tryptophan and tyrosine residues of the protein, with the alterations being comparatively higher for the tryptophans than the tyrosines. The interaction caused significant loss in the helicity of lysozyme, the change being higher with amaranth. The binding of both dyes was exothermic. The binding of amaranth was enthalpy driven, while that of tartrazine was predominantly entropy driven. Amaranth delayed lysozyme fibrillation at 25 µM, while tartrazine had no effect even at 100 µM. Nevertheless, both dyes had a significant inhibitory effect on fibrillogenesis. The present study explores the potential antiamyloidogenic property of these azo dyes used as food colorants.

Synthetic food additive dye "Tartrazine" triggers amorphous aggregation in cationic myoglobin.

Protein aggregation, a characteristic of several neurodegenerative diseases, displays vast conformational diversity from amorphous to amyloid-like aggregates. In this study, we have explored the interaction of tartrazine with myoglobin protein at two different pHs (7.4 and 2.0). We have utilized various spectroscopic techniques (turbidity, Rayleigh light scattering (RLS), intrinsic fluorescence, Congo Red and far-UV CD) along with microscopy techniques i.e. atomic force microscopy (AFM) and transmission electron microscopy (TEM) to characterize the tartrazine-induced aggregation in myoglobin. The results showed that higher concentrations of tartrazine (2.0-10.0mM) induced amorphous aggregation in myoglobin at pH 2.0 via electrostatic interactions. However, tartrazine was not able to induce aggregation in myoglobin at pH 7.4; because of strong electrostatic repulsion between myoglobin and tartrazine at this pH. The tartrazine-induced amorphous aggregation process is kinetically very fast, and aggregation occurred without the formation of a nucleus. These results proposed that the electrostatic interaction is responsible for tartrazine-induced amorphous aggregation. This study may help in the understanding of mechanistic insight of aggregation by tartrazine.

Food additives: Sodium benzoate, potassium sorbate, azorubine, and tartrazine modify the expression of NFκB, GADD45α, and MAPK8 genes.

It has been reported that some of the food additives may cause sensitization, inflammation of tissues, and potentially risk factors in the development of several chronic diseases. Thus, we hypothesized that expressions of common inflammatory molecules - known to be involved in the development of various inflammatory conditions and cancers - are affected by these food additives. We investigated the effects of commonly used food preservatives and artificial food colorants based on the expressions of NFκB, GADD45α, and MAPK8 (JNK1) from the tissues of liver. RNA was isolated based on Trizol protocol and the activation levels were compared between the treated and the control groups. Tartrazine alone could elicit effects on the expressions of NFκB (p = 0.013) and MAPK8 (p = 0.022). Azorubine also resulted in apoptosis according to MAPK8 expression (p = 0.009). Preservatives were anti-apoptotic in high dose. Sodium benzoate (from low to high doses) dose-dependently silenced MAPK8 expression (p = 0.004 to p = 0.002). Addition of the two preservatives together elicited significantly greater expression of MAPK8 at half-fold dose (p = 0.002) and at fivefold dose (p = 0.008). This study suggests that some of the food preservatives and colorants can contribute to the activation of inflammatory pathways.

Aspirin augments IgE-mediated histamine release from human peripheral basophils via Syk kinase activation.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, and food additives (FAs) may exacerbate allergic symptoms in patients with chronic idiopathic urticaria and food-dependent exercise-induced anaphylaxis (FDEIA). Augmentation of histamine release from human mast cells and basophils by those substances is speculated to be the cause of exacerbated allergic symptoms. We sought to investigate the mechanism of action of aspirin on IgE-mediated histamine release. METHODS: The effects of NSAIDs, FAs or cyclooxygenase (COX) inhibitors on histamine release from human basophils concentrated by gravity separation were evaluated. RESULTS: Benzoate and tartrazine, which have no COX inhibitory activity, augmented histamine release from basophils similar to aspirin. In contrast, ibuprofen, meloxicam, FR122047 and NS-398, which have COX inhibitory activity, did not affect histamine release. These results indicate that the augmentation of histamine release by aspirin is not due to COX inhibition. It was observed that aspirin augmented histamine release from human basophils only when specifically activated by anti-IgE antibodies, but not by A23187 or formyl-methionyl-leucyl-phenylalanine. When the IgE receptor signaling pathway was activated, aspirin increased the phosphorylation of Syk. Moreover, patients with chronic urticaria and FDEIA tended to be more sensitive to aspirin as regards the augmentation of histamine release, compared with healthy controls. CONCLUSIONS: Aspirin enhanced histamine release from basophils via increased Syk kinase activation, and that the augmentation of histamine release by NSAIDs or FAs may be one possible cause of worsening symptoms in patients with chronic urticaria and FDEIA.

Enhancement of prodigiosin production by Serratia marcescens TKU011 and its insecticidal activity relative to food colorants.

Prodigiosin (PG) has been reported to have various biological activities. With the aim of increasing Serratia marcescens TKU011 PG production on squid pen powder (SPP)-containing medium, the effects of phosphate and ferrous ion supplementation, autoclave treatment, and aeration were studied. Autoclave treatment showed positive results for PG productivity (2.48 mg/mL), which increased 2.5-fold when the organism was incubated in 50 mL of 40-min autoclaved medium in a baffle-based flask (250 mL) containing 1.5% SPP at 30 °C for 1 day and then at 25 °C for 2 additional days. Furthermore, the use of pigments including PG and the food colorants Allura Red AC (R40) and Tartrazine (Y4) as insecticides was also investigated. The lethal concentrations causing 50% Drosophila larval mortality (LC50) of PG, Y4, and R40 using a 5-d exposure period were 230, 449, and 30000 ppm, respectively. The results indicated that the biopigment PG and the food colorant Y4 were potentially toxic to Drosophila larvae.

Prolonged use of the food dye tartrazine (FD&C yellow no 5) and its effects on the gastric mucosa of Wistar rats.

Tartrazine is one of the most widely used artificial foods, drugs and cosmetic dyes. It 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. 45 male Wistar rats were assigned to a control group (A) or a treatment one (B). 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.

Prolonged use of the food dye tartrazine (FD&C yellow n° 5) and its effects on the gastric mucosa of Wistar rats

Tartrazine is one of the most widely used artificial foods, drugs and cosmetic dyes. It 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. 45 male Wistar rats were assigned to a control group (A) or a treatment one (B). The treatment group received 7.5 mg.kg-1.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.

O corante artificial tartrazina é um dos mais usados em todo o mundo para corar alimentos, medicamentos e cosméticos. É um derivado nitroso, sabidamente causador de reações alérgicas como asma e urticária, e tem sido alvo de estudos de mutagênese e carcinogênese por produzir a amina aromática ácido sulfanílico após ser metabolizado pela microflora gastrintestinal. Foram estudados 45 ratos Wistar, machos, divididos em grupo controle (A) e tratado (B). O grupo tratado recebeu o corante diariamente em água de beber ad libitum, na dose de 7,5 mg.kg-1.dia-1 por dez meses, do desmame aos doze meses de idade. Houve aumento significante do número de linfócitos e eosinófilos na mucosa do antro gástrico. Não foram observadas alterações carcinogênicas em nenhuma das regiões gástricas com a dose e o tempo utilizados. O corante tartrazina permanece entre os possíveis carcinógenos alimentares por ser da classe azo, devendo ter prosseguimento seus estudos; variando-se a dose e o tempo de administração e verificando-se seus efeitos quando associado a outros carcinógenos, para seu uso continuar sendo recomendado com segurança.

Influence of synthetic and natural food dyes on activities of CYP2A6, UGT1A6, and UGT2B7.

Synthetic or natural food dyes are typical xenobiotics, as are drugs and pollutants. After ingestion, part of these dyes may be absorbed and metabolized by phase I and II drug-metabolizing enzymes and excreted by transporters of phase III enzymes. However, there is little information regarding the metabolism of these dyes. It was investigated whether these dyes are substrates for CYP2A6 and UDP-glucuronosyltransferase (UGT). The in vitro inhibition of drug-metabolizing enzymes by these dyes was also examined. The synthetic food dyes studied were amaranth (food red no. 2), erythrosine B (food red no. 3), allura red (food red no. 40), new coccine (food red no. 102), acid red (food red no. 106), tartrazine (food Yellow no. 4), sunset yellow FCF (food yellow no. 5), brilliant blue FCF (food blue no. 1), and indigo carmine (food blue no. 2). The natural additive dyes studied were extracts from purple sweet potato, purple corn, cochineal, monascus, grape skin, elderberry, red beet, gardenia, and curthamus. Data confirmed that these dyes were not substrates for CYP2A6, UGT1A6, and UGT2B7. Only indigo carmine inhibited CYP2A6 in a noncompetitive manner, while erythrosine B inhibited UGT1A6 (glucuronidation of p-nitrophenol) and UGT2B7 (glucuronidation of androsterone). In the natural additive dyes just listed, only monascus inhibited UGT1A6 and UGT2B7.

Increased leukotriene production by food additives in patients with atopic dermatitis and proven food intolerance.

Recently, we identified a subgroup of patients with atopic dermatitis (AD) with a clinical relevant food intolerance proven by double blind placebo controlled challenge. In search of possible pathomechanisms involved in this food intolerance, which leads to aggravation of the disease, the aim of the present study was to determine sulfidoleukotriene production in these patients using isolated leucocytes from the peripheral blood after stimulation with different food additives. Leukotriene production of peripheral leucocytes was detected by incubation of isolated cells with the food additives at different concentrations ranging from 0.2 to 200 microg/mL after pre-stimulation with IL-3. Ten non-atopic donors (A), nine AD patients of the diet responder group with negative oral provocation test against food additives (B) and nine patients of the responder group with positive reactions after the oral provocation test (C) were investigated. In the non-atopic group (A), no increased sulfidoleukotriene (sLT) release was observed for all food additives tested. In group B, increased sLT production was determined using tartrazine in one patient (1/9) and using nitrite in two patients (2/9), whereas sLT production remained below the cut-off range in all patients of group B (9/9) using benzoate, metabisulfite and salicylate. By contrast, in group C increased sLT production was observed with food colour mix in 1/9, with tartrazine in 3/9, with benzoate in 4/9, with nitrite in 5/9, with salicylate in 2/9 and with metabisulfite in 1/9. However, no increased sLT concentration was determined in the presence of the tested food additives in two patients of group C. Increased sLT production by peripheral leucocytes in the presence of single food additives was observed in the majority of patients with a proven food intolerance towards food additives proven by double-blind-placebo-controlled challenges. These food additives were particulary tartrazine, benzoate and nitrite. These findings indicate that single food additives as aggravating factors in AD patients may trigger the disease through increased sLT production as a pathophysiological mechanism.

Tartrazine sensitivity.

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.

[Genotoxic study of commercial dyes with tartrazine base in S. typhimurium his- and E. coli trp-]. / Estudio genotóxico de colorantes comerciales con base Tartracina en S. typhimurium his- y E. coli trp-.

We study the genotoxic character of 21 food dyes samples with tartrazine in different trade-marks. Two homologated assays "in vitro" of reverse mutation in S. typhimurium and E. coli are used, with metabolic activation. There is no evidence of mutagenic character in any sample.

Sister chromatid exchange and chromosome aberrations induced by curcumin and tartrazine on mammalian cells in vivo.

Sister chromatid exchanges (SCEs) and chromosomal aberrations induced by curcumin (a natural dye) and tartrazine (a synthetic dye) were studied on bone marrow cells of mice and rats following acute and chronic exposure via the diet. Except for two low concentrations in the curcumin and one low concentration in the tartrazine treated series a significant increase in SCEs was observed in all the concentrations of the two dyes tested. Except for two high concentrations during the 9 months treatment no significant increase in chromosomal aberrations was observed in the curcumin treated series, whereas tartrazine showed a significant increase in chromosomal aberrations in some of the higher concentrations in all the series tested. The results indicate that tartrazine is more clastogenic than curcumin.

[Intragastric provocation and antigen-induced in vitro histamine liberation by the food additive E 102]. / Intragastrale Provokation und Antigeninduzierte Histaminfreisetzung in vitro mit Lebensmittelfarbstoff E 102.

Adverse reactions to tartrazine have been known since 1958. The mechanism of this reaction, a not IgE-mediated, anaphylactoid reaction, is not fully understood. The demonstration of this adverse reaction by provocative challenge feeding may be problematic by a score of subjective symptoms because of the placebo effect. This report deals with the intragastral provocation under endoscopic control with tartrazine and tartrazine-induced histamine release in vitro from gastric mucosa and from blood. Two patients with anamnestically suspected adverse reactions to tartrazine were studied. Correspondence of in vivo and in vitro testing with tartrazine could be demonstrated.