Absorption, Distribution and Excretion
... The fate of the pyrazole fragment of Tartrazine /was examined/ using sulphur-35 labelled Tartrazine and 1-(4-sulphophenyl)-3-methyl-4-(4-sulphophenylazo)-5-pyrazolone (SPMP an analogue of Tartrazine) and carbon-14 labeled SPMP. Following oral administration, both Tartrazine and SPMP labeled with sulphur-35 were predominantly excreted in feces (90 and 89 % of the dose respectively after 72 hours) with small amounts in urine (8 and 7.2 % of the dose, respectively, after 72 hours). The urinary radioactivity excreted in 48 hours with sulphanilic acid and 4-sulphophenylhydrazine was 23 and 23 % after Tartrazine administration, and 54 and 22 % after SPMP administration; the remaining radioactivity was not characterized.
... The metabolism of carbon-14 Tartrazine randomly labeled in the phenyl azo group /was studied/ in rat, rabbit and human. In both animal species Tartrazine was administered orally and intraperitoneally whilst humans received oral Tartrazine. ... After intraperitoneal administration to 6 rats of 2.4 mg/kg bw of Tartrazine, between 64 and 96 % of the dose was recovered unchanged in urine within 24 hours; no other products were reported. In rabbit, at a dose of 2.4 mg/kg bw of Tartrazine administered intraperitoneally, 94 % of the dose was recovered unchanged in urine within 24 hours, with a further 1.4 % recovered as conjugated sulphanilic acid. However, after an intraperitoneal dose of 1000 mg in the rabbit ... only 57.3% was recovered unchanged in urine within 24 hours, with a further 25.7 and 6 % recovered as free and conjugated sulphanilic acid, respectively. After oral administration to 3 rats at 5 mg/rat ..., no free Tartrazine was measured but means of 28 and 34.6 % were recovered in urine as free and conjugated sulphanilic acid, respectively. In the rabbit dosed 1000 mg ... 8.2 % was recovered unchanged in urine within 24 hours with a further 27 and 26.8 % as free and conjugated sulphanilic acid respectively within 72 hours. In 4 humans receiving a single capsule containing 89-100 mg of Tartrazine ..., no free Tartrazine was measured in urine for any subject; in one subject 106 % was recovered as free sulphanilic acid whilst for the other 3 subjects mean recoveries of free and conjugated sulphanilic acid were 40.6 and 49.7 % respectively. ...
Low biliary excretion of Tartrazine (1 %) /was demonstrated/ following intravenous administration of an unspecified dose. ... low biliary excretion was due to the carboxyl group. After a dose of 2 mg ... unchanged Tartrazine could be detected in bile, but there was no evidence of ring fission products. Following intraperitoneal injection, an unidentified and unquantified Tartrazine conjugate was rapidly excreted in bile, but again none of the previously reported reductive ring fission products.

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Metabolism / Metabolites
After oral administration there is extensive metabolism of Tartrazine by the gastrointestinal microflora to sulphanilic acid and aminopyrazalone (which may then be subsequently cleaved to sulphanilic acid and alpha-amino-beta-ketobutyric acid fragments with the latter breaking down further via intermediary metabolism with release of carbon dioxide).
Absorption and metabolism of (14)C-labelled tartrazine (FD & C Yellow No. 5) and high molecular weight polymeric derivatives were compared in rats. A trace to 1.5% of unchanged monomeric dyes was excreted in urine and bile during the first 24 hr after dosing. No unchanged dye was absorbed after administration of the polymeric derivatives. ...In animals dosed with tartrazine and its polymer derivative, absorption of the cleavage product aminopyrazolone and its metabolites was 4.0 and 4.6%, respectively. Azo bond cleavage did not appear to be decreased in the polymer derivatives. However, the sulphanilic acid moiety of both dyes remained attached to the polymer backbone, resulting in a 95% decrease in sulphanilic acid absorption with polymeric tartrazine.
The 4-sulphophenylhydrazine metabolite was also labeled with sulphur-35 and administered orally and intraperitoneally. Excretion of this metabolite differed with the route of administration (35 and 49 % in urine and feces, respectively, 48 hours following oral, and 90 and 5 % in urine and feces, respectively, 48 hours following intraperitoneal administration). Following oral administration, 69 % of urinary radioactivity excreted in 48 hours was sulphanilic acid and 21 % was 4-sulphophenylhydrazine, whereas following intraperitoneal administration, 9 % of urinary radioactivity excreted in 48 hours was sulphanilic acid and 73% was 4-sulphophenylhydrazine. These data suggest there is a marked conversion of 4- sulphophenylhydrazine to sulphanilic acid presumably in the gut lumen. /4-sulphophenylhydrazine/

Interactions
In 2006, the Korea Food and Drug Administration reported that combinations of dietary colors such as allura red AC (R40), tartrazine (Y4), sunset yellow FCF (Y5), amaranth (R2), and brilliant blue FCF (B1) are widely used in food manufacturing. Although individual tar food colors are controlled based on acceptable daily intake (ADI), there is no apparent information available for how combinations of these additives affect food safety. In the current study, the potencies of single and combination use of / allura red AC, tartrazine, sunset yellow FCF, amaranth, and brilliant blue FCF / were examined on neural progenitor cell (NPC) toxicity, a biomarker for developmental stage, and neurogenesis, indicative of adult central nervous system (CNS) functions. /allura red AC/and /amaranth/ reduced NPC proliferation and viability in mouse multipotent NPC, in the developing CNS model. Among several combinations tested in mouse model, combination of /tartrazine/ and /brilliant blue FCF/ at 1000-fold higher than average daily intake in Korea significantly decreased numbers of newly generated cells in adult mouse hippocampus, indicating potent adverse actions on hippocampal neurogenesis. However, other combinations including /allura red AC/ and /amaranth/ did not affect adult hippocampal neurogenesis in the dentate gyrus. Evidence indicates that single and combination use of most tar food colors may be safe with respect to risk using developmental NPC and adult hippocampal neurogenesis. However, the response to excessively high dose combination of /tartrazine/and /brilliant blue FCF/ is suggestive of synergistic effects to suppress proliferation of NPC in adult hippocampus. Data indicated that combinations of tar colors may adversely affect both developmental and adult hippocampal neurogenesis...
The release of histamine from purified rat peritoneal mast cells induced by specific antigen (egg albumin), compound 48/80 and calcium ionophore A23187 was modified by tartrazine. Histamine release induced by 48/80 and antigen was inhibited by the presence of 1x10-5 to 1x10-2 M tartrazine. The inhibitory effect on egg albumin induced histamine release was maximal when the tartrazine was added simultaneously with egg albumin, and was reduced by increased preincubation of the cells with tartrazine. Tartrazine had a small inhibitory effect on ionophore induced release at high concentrations, but augmented histamine release at tartrazine concentrations of 1x10-3 and 1x10-4 M. Augmentation of ionophore induced release was maximal at between 0-5 min preincubation of the cells with tartrazine.

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Non-Human Toxicity Values
LD50 Rat oral > 2000 mg/kg bw
LD50 Mouse oral 12,750 mg/kg bw
LD50 Rat iv 1,000 mg/kg bw
LD50 Rat ip >2.0 g/kg bw

C.i. pigment yellow 100 is a yellow to greenish-yellow powder. (NTP, 1992)
Tartrazine is an organic sodium salt which is the trisodium salt of tartrazine acid. A synthetic lemon yellow azo dye used as a food colouring. It has a role as a histological dye and a food colouring. It contains a tartrazine(3-).
An anionic, hydrophilic azo dye with an orange-yellow color used in fabrics, foods and cosmetics, and as a biological stain.

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Mechanism of Action
... Blocking studies showed that tartrazine contraction was inhibited by atropine alone but not by any other blocking agent tested, implying that tartrazine acts either directly or indirectly upon the muscarinic acetylcholine receptor associated with parasympathetic innervation.
The ability of selected food colors to interact with isolated guinea-pig ileum was investigated using a gut bath system. Studies revealed that guinea-pig ileum was specifically sensitive to tartrazine. Intestinal contraction occurred dose-dependently down to a minimum effective dose of 10 uM. ...Studies investigating the biological activity of structural analogues of tartrazine revealed the ability to initiate intestinal contraction was associated with the presence of the carboxylic acid residue at the R1 position of the pyrazole ring. Blocking studies showed that tartrazine contraction was inhibited by atropine alone but not by any other blocking agent tested, implying that tartrazine acts either directly or indirectly upon the muscarinic acetylcholine receptor associated with parasympathetic innervation.

C16H9N4NA3O9S2

534.3634

533.95

1934-21-0

34175-08-1 (parent);74920-66-4 (barium salt);84681-80-1 (barium salt (2:3))

164825

Pink to red solid powder

1.93 g/cm3 (20ºC)

300ºC

2.781

0

12

3

34

949

0

UJMBCXLDXJUMFB-UHFFFAOYSA-K

InChI=1S/C16H12N4O9S2.3Na/c21-15-13(18-17-9-1-5-11(6-2-9)30(24,25)26)14(16(22)23)19-20(15)10-3-7-12(8-4-10)31(27,28)29;;;/h1-8,13H,(H,22,23)(H,24,25,26)(H,27,28,29);;;/q;3*+1/p-3

trisodium;5-oxo-1-(4-sulfonatophenyl)-4-[(4-sulfonatophenyl)diazenyl]-4H-pyrazole-3-carboxylate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~50 mg/mL (~93.57 mM)
H2O : ~50 mg/mL (~93.57 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.68 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 2: 16.67 mg/mL (31.20 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)