Absorption, Distribution and Excretion
Of FD&C Red No.2 administered orally 10% appear in the urine and 43% in the feces (accounting for 53%). Part of the absorbed reduction product is further metabolized to unknown products
A single oral dose of 50 mg per animal was administered to four rats. Only 2.8% was absorbed from the gastro-intestinal tract; the metabolites in the urine and bile were predominantly products resulting from the reductive fission of the azo-linkage, such as 1-amino-4-naphthalene sulfonic acid and 1-amino-2-hydroxy-3,6-naphthalene disulfonic acid. The former compound was found also in the feces.
The absorption and elimination of 1-amino-4-naphthalene-sulfonic acid, one of the azo-reduction products in rats were examined after dosing by gavage, in drinking-water and mixed into the diet. Little is metabolized by mammalian liver azo-reductase systems, almost all reduction occurring through gut microflora. 1-amino-2-hydroxy-3,6-naphthalene sulfonic acid was not studied as it is not well absorbed.
1-Amino-4-naphthalene sulfonic acid, one of the metabolites of amaranth, is absorbed to the extent of 18% after its oral administration.
For more Absorption, Distribution and Excretion (Complete) data for AMARANTH (12 total), please visit the HSDB record page.

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Metabolism / Metabolites
2-Hydroxy-1-(p-sulfophenylazo)naphthalene-3,6-disulfonic acid yields 1-amino-2-hydroxynaphthalene-3,6-disulfonic acid in Escherichia and Proteus; 1-naphthylamine-4-sulfonic acid in Escherichia and Proteus.
The mechanism of the azo reduction of sulfonazo III and amaranth by the rat hepatic monooxygenase system was studied. Air strongly inhibited (greater than 95%) the enzymatic reduction of both azo compounds; a 100% CO atmosphere inhibited amaranth reduction (greater than 90%) but only slightly inhibited sulfonazo III reduction (13%). The addition of 50 microM sulfonazo III to microsomal incubations stimulated oxygen consumption, NADPH oxidation, and adrenochrome formation, whereas 100 microM amaranth did not. The reduction potentials of these two azo compounds were also very different (amaranth, E = -0.620 V; sulfonazo III, E = -0.265 V versus normal hydrogen electrode). The organic mercurial mersalyl converted cytochrome P-450 to cytochrome P-420 (68%) and markedly decreased NADPH-cytochrome P-450(c) reductase activity (97%) in microsomal preparations, presumably by inactivating or destroying functional sulfhydryl groups important for the catalytic activity of these enzymes. GSH was used to restore, and NADP+ to protect, the activities of the monooxygenase components from the effects of mersalyl. The data indicate that inactivation of NADPH-cytochrome P-450(c) reductase inhibits sulfonazo III and amaranth reduction, whereas inactivation of cytochrome P-450 inhibits only amaranth reduction. Furthermore, the reduction of sulfonazo III by purified microsomal NADPH-cytochrome P-450(c) reductase was significantly faster than the rate of reduction of amaranth. These studies demonstrate that two distinct sites of azo reduction exist in the monooxygenase system and that not all azo compounds are reduced by cytochrome P-450.
The liver enzyme that reduces azo-linkages plays little part in the metabolism /of rats/, as was shown in experiments in which the amaranth was given by intrasplenic infusion. Reduction of the compound is therefore most probably affected by the intestinal bacteria.
Amaranth is rapidly reduced by a suspension of bacteria obtained from large intestine and cecum of rats. /Investigators/ found that it is reduced by rat liver homogenates as well as by rat intestinal contents. Products of reductive cleavage of amaranth, namely, 1-amino-4-naphthalene sulfonic acid and 1-amino-2-hydroxy-3,6-naphthalene disulfonic acid (R-amino salt), are found in urine of rats fed the color.
For more Metabolism/Metabolites (Complete) data for AMARANTH (6 total), please visit the HSDB record page.

Interactions
... In the current study, the potencies of single and combination use of allura red AC (R40), tartrazine (Y4), sunset yellow FCF (Y5), amaranth (R2), and brilliant blue FCF (B1) were examined on neural progenitor cell (NPC) toxicity, a biomarker for developmental stage, and neurogenesis, indicative of adult central nervous system (CNS) functions. R40 and R2 reduced NPC proliferation and viability in mouse multipotent NPC, in the developing CNS model. Among several combinations tested in mouse model, combination of Y4 and B1 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 R40 and R2 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 Y4 and B1 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; thus, further extensive studies are required to assess the safety of these additive combinations.
Two groups of 100 mice received either 0 or 0.01 g amaranth paste (= 0.004 g amaranth) by gavage daily. One drop of either 9,10-dimethyl-2-benzanthracene or 3,4-benzopyrene was applied once per week to interscapular skin. Papillomata appeared 3.5 weeks earlier in test animals and in a greater number of animals. A larger percentage became malignant in test animals.
Cholestyramine at 2.5% suppl level counteracted toxic effects produced in rats by addition of 5% amaranth to their purified, low-fiber diet.
Mutagenic activity of beta-naphthylamine was suppressed in presence of amaranth. Similar results /have been/ reported with alpha-naphthylamine suggesting that amaranth interacts with liver-activation system to prevent conversion of amine to mutagen.

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Non-Human Toxicity Values
LD50 Mouse ip 1000 mg/kg
LD50 Rat iv 1 g/kg
LD50 Rat ip 1 g/kg
LD50 Mouse oral >10 g/kg bw
LD50 Rat oral 6 g/kg bw

Amaranth is a dark red to dark purple powder. Almost no odor. Tastes salty. pH (1% solution in water) approximately 10.8. Used to dye wool and silk bright bluish-red from an acid bath.
Amaranth is an organic molecular entity.
A sulfonic acid-based naphthylazo dye used as a coloring agent for foodstuffs and medicines and as a dye and chemical indicator. It was banned by the FDA in 1976 for use in foods, drugs, and cosmetics. (From Merck Index, 11th ed)

C20H11N2NA3O10S3

604.4613

603.926

915-67-3

13506

Brown to reddish brown solid powder

1.5

>300°C

44ºC

6.068

1

12

2

38

1080

0

WLDHEUZGFKACJH-UHFFFAOYSA-K

InChI=1S/C20H14N2O10S3.3Na/c23-20-18(35(30,31)32)10-11-9-12(33(24,25)26)5-6-13(11)19(20)22-21-16-7-8-17(34(27,28)29)15-4-2-1-3-14(15)16;;;/h1-10,23H,(H,24,25,26)(H,27,28,29)(H,30,31,32);;;/q;3*+1/p-3

sodium (E)-3-hydroxy-4-((4-sulfonatonaphthalen-1-yl)diazenyl)naphthalene-2,7-disulfonate

Amaranth DyeE123E 123E-123Azo

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 : ~25 mg/mL (~41.36 mM)
H2O : ~6.67 mg/mL (~11.03 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.14 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (4.14 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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 (Please use freshly prepared in vivo formulations for optimal results.)