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Indigo carmine
Indigo carmine
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Indigo carmine
Names
Preferred IUPAC name
Disodium [2(2′)E]-3,3′-dioxo-1,1′,3,3′-tetrahydro[2,2′-biindolylidene]-5,5′-disulfonate
Other names
  • indigotine
  • 5,5′-indigodisulfonic acid sodium salt
  • Brilliant Indigo
  • 4 G
  • C.I. Acid Blue 74
  • C.I. 73015
  • CI Food Blue 1
  • FD&C Blue 2
  • Sicovit Indigotin 85
  • E132
  • indigotindisulfonate sodium
  • Caustic Blue
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.011.572 Edit this at Wikidata
EC Number
  • 212-728-8
E number E132 (colours)
KEGG
UNII
  • InChI=1S/C16H10N2O8S2.2Na/c19-15-9-5-7(27(21,22)23)1-3-11(9)17-13(15)14-16(20)10-6-8(28(24,25)26)2-4-12(10)18-14;;/h1-6,17-18H,(H,21,22,23)(H,24,25,26);;/q;2*+1/p-2/b14-13+;; checkY
    Key: KHLVKKOJDHCJMG-QDBORUFSSA-L checkY
  • InChI=1/C16H10N2O8S2.2Na/c19-15-9-5-7(27(21,22)23)1-3-11(9)17-13(15)14-16(20)10-6-8(28(24,25)26)2-4-12(10)18-14;;/h1-6,17-18H,(H,21,22,23)(H,24,25,26);;/q;2*+1/p-2/b14-13+;;
    Key: KHLVKKOJDHCJMG-AKPRSONXBD
  • [Na+].[Na+].[O-]S(=O)(=O)c3cc4C(=O)\C(=C2\C(=O)c1cc(ccc1N2)S([O-])(=O)=O)Nc4cc3
Properties
C16H8N2Na2O8S2
Molar mass 466.36 g/mol
Appearance purple solid
Melting point >300 °C (572 °F)
10 g/L (25 °C (77 °F))
Hazards
GHS labelling:
GHS07: Exclamation mark[1]
Warning
H302[1]
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
2
1
0
Pharmacology
V04CH02 (WHO)
Legal status
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)
Indigotindisulfonate sodium
Container of indigotindisulfonate sodium for medical use
Clinical data
Trade namesBludigo
License data
Identifiers
E numberE132 (colours) Edit this at Wikidata
CompTox Dashboard (EPA)
ECHA InfoCard100.011.572 Edit this at Wikidata

Indigo carmine, or 5,5′-indigodisulfonic acid sodium salt, is an organic salt derived from indigo by aromatic sulfonation, which renders the compound soluble in water. Like indigo, it produces a blue color, and is used in food and other consumables, cosmetics, and as a medical contrast agent and staining agent; it also acts as a pH indicator. It is approved for human consumption in the United States and European Union.[3][4] It has the E number E132, and is named Blue No. 2 by the US Federal Food, Drug, and Cosmetic Act.[5]

Uses

[edit]
Indigo Carmine (pH indicator)
below pH 11.4 above pH 13.0
11.4 ⇌ 13.0
Experiment using indigo carmine as an indicator

Indigo carmine in a 0.2% aqueous solution is blue at pH 11.4 and yellow at 13.0. Indigo carmine is also a redox indicator, turning yellow upon reduction. Another use is as a dissolved ozone indicator[6] through the conversion to isatin-5-sulfonic acid.[6] This reaction has been shown not to be specific to ozone: it also detects superoxide, an important distinction in cell physiology.[7] It is also used as a dye in the manufacturing of pharmaceutical capsules.

Medical uses

[edit]

Indigotindisulfonate sodium, sold under the brand name Bludigo, is used as a contrast agent during surgical procedures.[2] It is indicated for use in cystoscopy in adults following urological and gynecological procedures.[2][8] It was approved for medical use in the United States in July 2022.[specify][2][8]

In obstetric surgery, it may be used to detect amniotic fluid leaks. In urologic surgery, intravenous indigo carmine can be used to highlight portions of the urinary tract. The dye is filtered rapidly by the kidneys from the blood, and colors the urine blue. However, the dye can cause a potentially dangerous acute increase in blood pressure in some cases.[9]

Indigo carmine stain is not absorbed into cells, so it is applied to tissues to enhance the visibility of mucosa. This leads to its use for examination and diagnosis of benign and malignant lesions and growths on mucosal surfaces of the body.[10]

Food, pharmaceutical, cosmetic, and scientific uses

[edit]

Indigo carmine is one of the few blue food colorants. Others include the anthocyanidins and rare substances such as variegatic acid and popolohuanone.[11]

Safety and regulation

[edit]

Indigo carmine shows "genotoxicity, developmental toxicity or modifications of haematological parameters in chronic toxicity studies". Only at 17 mg/kg of body weight per day were effects on testes observed.[12]

References

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Indigo carmine

View on Grokipedia
from Grokipedia
Indigo carmine, also known as indigotindisulfonate sodium or FD&C Blue No. 2, is a synthetic dye derived from through sulfonation, characterized by the chemical formula C₁₆H₈N₂Na₂O₈S₂ and a molecular weight of 466.35 g/mol. It appears as a dark or purplish- powder that dissolves in to form a vibrant solution, with partial solubility in alcohol and limited solubility in organic solvents. Primarily utilized as a colorant, it serves as the E 132 in the and is approved for use in various consumables, , and medical applications, though it has raised safety concerns due to potential and adverse effects. Synthesized commercially by sulfonating natural or synthetic indigo—often via fusion of N-phenylglycine with sodamide and alkali hydroxides under ammonia pressure—indigo carmine exhibits stability as a pH and redox indicator, turning from blue to yellow in alkaline conditions. In the food industry, it is added to products like candies, beverages, and pet foods to achieve a deep blue hue, with maximum permitted levels set at 500 mg/kg in many jurisdictions; the European Food Safety Authority (EFSA) has established an acceptable daily intake (ADI) of 5 mg/kg body weight for material of at least 93% purity, based on studies showing no adverse effects up to 500 mg/kg body weight per day in animal models, and exposure assessments indicate no safety concern at reported use levels and within maximum permitted levels. Medically, it functions as a diagnostic agent, particularly in urology and gynecology, where intravenous administration (typically 40 mg in 5 mL) aids in visualizing ureteral patency during cystoscopy or detecting tissue lesions in chromoendoscopy and surgical procedures. It is also employed as a histological stain and, in electrochemistry, as a material for positive electrodes in batteries. Despite its utility, indigo carmine is considered moderately toxic, with reported adverse effects including nausea, vomiting, diarrhea upon ingestion; skin and eye irritation on contact; and, upon injection, cardiovascular issues such as hypotension, hypertension, bradycardia, or rare arrhythmias. Allergic reactions like urticaria, bronchospasm, and swelling have been documented, particularly in sensitive individuals, and concerns persist regarding potential genotoxicity from impurities like unsulfonated aromatic amines or UV-degraded products, though in vivo studies show low absorption and no clear carcinogenicity at approved doses. Regulatory bodies emphasize the need for high-purity formulations, and alternatives such as methylene blue or virtual chromoendoscopy techniques are sometimes recommended to mitigate risks; as of April 2025, the US FDA announced plans to phase out all petroleum-based synthetic food dyes, including FD&C Blue No. 2, by the end of 2026, while the EU authorized its use as a feed additive for cats, dogs, and ornamental fish in the same month.

Chemical properties

Molecular structure

Indigo carmine is the disodium salt of indigo-5,5'-disulfonic , possessing the C16_{16}H8_{8}N2_{2}Na2_{2}O8_{8}S2_{2}. Its molecular weight is 466.35 g/mol. The IUPAC name is disodium (2E)-3-oxo-2-(3-oxo-5-sulfonato-1H-indol-2-ylidene)-1H-indole-5-sulfonate. The molecular structure consists of two indolinone (or indole-2,3-dione) rings linked by a central carbon-carbon at their 2-positions, with keto groups at the 3-positions of each ring and groups (-SO3_{3}Na) attached to the 5-positions of the portions of the rings. This arrangement forms a planar, responsible for its characteristic blue color in solution, where the conjugation between the rings and the electron-withdrawing groups stabilize the . Indigo carmine serves as a synthetic analog of natural , a extracted from plants such as , but it is produced through sulfonation of indigo at the 5 and 5' positions, which introduces the groups to improve while retaining the core bis-indole framework.

Physical characteristics

Indigo carmine is typically observed as a deep to dark purple powder or crystalline solid. When dissolved in , it produces a vibrant blue solution characteristic of its use in various applications. The compound exhibits high solubility in water, approximately 10 g/L at 25°C, owing to the sulfonate groups enhancing its hydrophilic nature, while it is slightly soluble in ethanol, insoluble in acetone and most other organic solvents. Its density is approximately 0.71 g/cm³ (bulk density at 29°C). Indigo carmine decomposes at temperatures above 300°C without undergoing melting. In terms of pH stability, indigo carmine remains stable and retains its color in acidic to neutral solutions ( 4-7). However, in strong alkaline conditions, its color fades or shifts. It functions as a , transitioning from to yellow over the range of 11.4-14. Optically, it absorbs maximally at around 610 nm, accounting for its distinctive hue.

Chemical reactivity

Indigo carmine demonstrates significant stability under neutral conditions, where it resists oxidation effectively. However, it is susceptible to reduction by agents such as , converting to its colorless leuco form through a two-step process involving direct interaction with the reductant. This transformation highlights its properties, featuring a reversible cycle between the oxidized form and the reduced yellowish leuco form, which underpins its role as a indicator in . The compound exhibits poor , undergoing under UV exposure that leads to gradual color loss and structural breakdown. Aqueous solutions of indigo carmine also fade upon prolonged standing in light, emphasizing its sensitivity to photolytic processes. Due to its two groups, indigo carmine behaves as a strong acid in its protonated form, though it is typically used as the disodium salt. It functions as a with a color transition from blue at 11.5 to yellow at 14.0, corresponding to a pKa of approximately 12.8 for the relevant event. Additionally, indigo carmine is incompatible with strong oxidizing agents like or , which induce decomposition and discharge its color.

Production

Synthesis methods

Indigo carmine, also known as disodium 5,5'-indigotindisulfonate, is primarily synthesized through the sulfonation of , a process that introduces two groups at the 5 and 5' positions of the indigo molecule. The classical method employs fuming () as the sulfonating agent, where indigo is heated in oleum at temperatures ranging from 80 to 100°C for several hours to form indigo disulfonic acid. This reaction leverages the facilitated by the excess in oleum, targeting the electron-rich positions on the indigo structure. Following sulfonation, the reaction mixture is diluted with to precipitate unreacted indigo, and the disulfonic acid is isolated before neutralization with to yield the water-soluble disodium salt. The key reaction steps can be summarized as follows:
  1. Sulfonation: Indigo reacts with to produce indigo disulfonic acid. \ceC16H10N2O2+2H2SO4−>C16H8N2O2(SO3H)2+2H2O\ce{C16H10N2O2 + 2 H2SO4 -> C16H8N2O2(SO3H)2 + 2 H2O}
  2. Neutralization: The disulfonic acid is treated with to form the disodium salt. \ceC16H8N2O2(SO3H)2+2NaOH−>C16H8N2O2(SO3Na)2+2H2O\ce{C16H8N2O2(SO3H)2 + 2 NaOH -> C16H8N2O2(SO3Na)2 + 2 H2O}
These steps are typically conducted under controlled conditions to ensure at the 5,5' positions. Alternative synthetic routes begin with precursors to , followed by sulfonation. One such pathway starts from indoxyl, which is oxidized—often using air or chemical oxidants—to form , and the resulting is then sulfonated as in the classical method. Another route involves the oxidative coupling of using in the presence of a catalyst to generate , which is subsequently sulfonated. A third approach uses N-phenylglycine, which undergoes self-coupling with and a base under pressure to produce , followed by sulfonation. These routes allow for the use of synthetic starting materials, bypassing natural extraction. The product is purified by methods such as with to precipitate the sodium salt, followed by and recrystallization from or aqueous alcohol to achieve high purity levels exceeding 99%. Early synthesis methods relied heavily on , which generated significant waste due to excess and byproducts. Modern approaches emphasize greener alternatives, such as using concentrated without fuming agents or steps in precursor synthesis to minimize environmental impact and reduce .

Commercial production

Indigo carmine is primarily produced on an industrial scale through the sulfonation of synthetic indigo, which is itself manufactured from derivatives via established chemical processes. The production is integrated with indigo synthesis facilities, where indigo powder is reacted with concentrated in continuous flow reactors at elevated temperatures (typically 90-110°C) to introduce groups at the 5 and 5' positions. This step is followed by neutralization with , precipitation, filtration to remove impurities, and drying to yield the disodium salt. Major global production occurs in , with key manufacturers including Gogia Chemical Industries Pvt. Ltd. and Colourchem Pvt. Ltd. in , Wuxi Ding Tai Chemical Co., Ltd. and Damao Chemical Reagent Factory in , and Sensient Colors LLC . Annual global production of indigo carmine is estimated at approximately 3,000 to 4,000 metric tons as of 2025, driven by demand in , pharmaceutical, and sectors. Emerging biotechnological methods using recombinant for production aim to enhance , potentially reducing the by 30-50%. Quality standards are stringent, particularly for end-use applications. USP-grade indigo carmine requires 96.0-102.0% sodium indigotindisulfonates on the dried basis and compliance with specifications for (λ_max 608-612 nm) and absence of , ensuring suitability for medical diagnostics. Food-grade material adheres to E132 () or FD&C Blue No. 2 () regulations, mandating at least 85% total color with limits on (<3 ppm) and lead (<10 ppm) to meet safety thresholds for ingestion. Environmental considerations in commercial production focus on managing acidic effluents from sulfonation, which contain byproducts and residual . Producers implement via neutralization and to achieve discharge limits (e.g., 6-9, <500 mg/L), often using biological aerated filters. There is a growing shift toward sustainable indigo feedstocks, including biotechnological routes using engineered to reduce reliance on petrochemical-derived , potentially lowering the by 30-50% compared to traditional synthesis.

History

Discovery

Indigo, the natural precursor to indigo carmine, has been utilized as a textile dye since approximately 4000 BCE, with archaeological evidence from ancient and indicating its extraction from plants of the genus for coloring fabrics. This early use established as one of the oldest known dyes, valued for its vibrant hue and fastness properties. The specific compound indigo carmine, a water-soluble sulfonated derivative of known chemically as 5,5'-indigodisulfonic acid disodium salt, was first isolated in 1743 by German lawyer and Christian Barth. Barth achieved this by treating natural with concentrated , producing a powder initially called "Saxon Blue" for its application in wool and . This semi-synthetic process marked the earliest known method to enhance indigo's solubility, enabling broader industrial use while relying on plant-derived starting material. In the 1880s, German chemist advanced the understanding of indigo's chemistry by elucidating its molecular structure in 1883, building on earlier attempts and proposing sulfonation as a key modification for derivative compounds like indigo carmine. Baeyer's work laid the groundwork for synthetic production, though practical synthesis of indigo itself was first accomplished by Karl Heumann in 1890 via fusion of N-phenylglycine, leading to water-soluble variants including sulfonated forms by the late 1890s. The term "carmine" in indigo carmine draws an analogy to carminic acid, the red dye from cochineal insects, reflecting a historical convention for naming vivid organic colorants, while the full designation indigotindisulfonate emerged with early 20th-century patents for purified versions.

Development and early commercialization

Indigo carmine, initially developed as a semi-synthetic dye from natural indigo in the 18th century, saw significant industrial scaling in the early 20th century through fully synthetic production methods. Following Adolf von Baeyer's elucidation of indigo's structure in 1883 and BASF's commercial launch of synthetic indigo in 1897, companies like BASF and Farbwerke Hoechst advanced sulfonation processes to produce indigo carmine on a large scale, enabling its widespread use as a textile dye that replaced inconsistent natural variants. By the 1910s and 1920s, IG Farben, formed from the merger of BASF and other firms in 1925, further optimized production for the dye industry, contributing to the decline of natural indigo extraction as synthetic alternatives proved more reliable and cost-effective. In , indigo carmine gained adoption in the early as a urological for visualizing ureteral patency during surgeries, first introduced in by Voelcher and through advancements in endoscopic techniques pioneered by early urologists. Its intravenous administration allowed for clear differentiation of urinary structures, marking a key shift toward synthetic dyes in diagnostic procedures. Early formulations faced purity challenges, with impurities from incomplete sulfonation leading to instability and inconsistent coloring; by the late , reformulations improved and reduced oxidative degradation, enhancing its reliability for clinical use. Food applications emerged in the 1930s with approvals in for use in and beverages, leveraging its vibrant hue for product appeal. In the United States, the FDA certified it as FD&C Blue No. 2 in the early among the original synthetic colors, with permanent listing under the 1938 Federal Food, Drug, and Cosmetic Act. By the 1950s, the near-complete transition to synthetic production amid the natural market's collapse solidified its role in global . In the , international as E132 under European regulations facilitated broader commercialization, establishing uniform quality and safety benchmarks.

Applications

Medical applications

Indigo carmine is primarily administered intravenously as a diagnostic agent during to visualize and identify ureteral orifices through the blue staining of . The standard dosage is 5 mL of a 0.8% solution (equivalent to 40 mg), which is sufficient for adults and allows for rapid assessment of ureteral patency in procedures such as those following gynecologic surgeries. This application leverages the dye's ability to highlight the efflux of blue-colored from the ureteral openings, aiding surgeons in confirming the of the urinary tract. In surgical contexts, indigo carmine is used to detect urinary tract fistulas and injuries, particularly after hysterectomies, by intravenous injection to observe leakage or absence of efflux indicating obstruction or damage. The is typically given at the same 5 mL dose intraoperatively, enabling immediate evaluation during to identify potential complications like vesicovaginal fistulas or ureteral transections. This method supports timely intervention, reducing the risk of postoperative urinary issues. The involves rapid renal , with the appearing in the within 5 to 10 minutes after injection in patients with normal function, with the coloration typically observable during the procedure and clearing rapidly due to quick renal elimination. It is not significantly metabolized and is primarily eliminated unchanged via glomerular filtration, providing a short of 4 to 5 minutes that favors its use in intraoperative settings. This quick clearance ensures transient visualization without prolonged interference in subsequent procedures. Clinically, indigo carmine demonstrates high efficacy in assessing ureteral patency, with sensitivity rates around 94-95% and specificity exceeding 99% in detecting obstructions during . Compared to alternatives like , indigo carmine is preferred in due to its reliable excretion without metabolic conversion to a colorless form, offering clearer visualization despite occasional supply shortages prompting the use of substitutes.

Food and cosmetic applications

Indigo carmine, known as E132 in the and FD&C Blue No. 2 , serves as a synthetic color additive in various products to impart a vibrant hue. It is commonly used in candies, , soft drinks, baked goods, jams, and pet s, where it enhances visual appeal without altering flavor. In the , maximum permitted levels (MPLs) for E132 range from 50 to 500 mg/kg depending on the category, such as 500 mg/kg in non-alcoholic flavored drinks and . In the US, it is certified for use in foods in amounts consistent with current (GMP), as determined safe by the FDA. The dye's high allows for even dispersion in liquid and semi-solid products, contributing to its utility in acidic beverages where it helps maintain color stability. In cosmetics, indigo carmine provides blue tones in products intended for direct skin or hair contact, including hair dyes, soaps, shampoos, and nail polishes. In the US, it must be listed as an artificial color on product labels for both food and cosmetics. However, due to concerns over potential links to hyperactivity in children, indigo carmine is banned in Norway and restricted in some other countries. Regarding product stability, indigo carmine retains its blue color effectively within a range of 3 to 7, making it suitable for many and cosmetic formulations. It performs well in stabilizing hues in acidic environments like soft drinks but can fade upon prolonged exposure to or , necessitating protective or stabilizers in commercial products.

Industrial applications

Indigo carmine serves as an in the , primarily for coloring and fabrics, though its use is constrained by poor and washfastness properties. It is also applied in the manufacturing of inks and for imparting hues to products. These applications leverage its vibrant color but are increasingly supplemented by more durable synthetic alternatives. In laboratory settings, indigo carmine functions as a biological stain for microscopic analysis, effectively highlighting structures such as in animal tissues and aiding in the visualization of cellular components. Its properties enable it to act as a reliable indicator in , undergoing reversible color changes from (oxidized) to colorless or (reduced) forms during reactions. Additionally, it is incorporated into pH testing kits, shifting from to in the range of 11.5 to 14.0. Beyond textiles and labs, indigo carmine finds utility in other industrial sectors, including analytical chemistry for spectrophotometric determinations where its strong absorption in the visible spectrum facilitates quantitative analysis. In metallurgy, it is employed as a reagent to form complexes with copper(II) ions, supporting processes such as ion detection in plating baths and related electrochemical applications. It is also used in electrochemistry, such as in materials for positive electrodes in certain battery types. Overall, non-food and non-medical industrial uses account for a notable but diminishing portion of global production. Its advantages in these contexts include low cost and relative non-toxicity when used in dilute solutions for research and manufacturing.

Safety and regulation

Toxicology and adverse effects

Indigo carmine exhibits low oral , with absorption estimated at less than 1% of the administered dose in , primarily due to its poor in . The majority of an oral dose is excreted unchanged in the , while biliary accounts for only about 0.004% in rats. In contrast, intravenous administration results in rapid renal clearance via tubular , with a plasma of approximately 4-12 minutes and most of the dose eliminated unchanged in the within 2 hours. Acute adverse effects of indigo carmine are primarily associated with intravenous use and include rare reactions such as , , and . Severe anaphylactic reactions occur infrequently, with only isolated case reports documented, and an estimated incidence of severe below 0.07% for blue dyes including indigo carmine. Hemodynamic instability, manifesting as or, less commonly, , has also been reported in a small number of cases following IV injection, potentially linked to serotonergic effects or direct vascular responses. Oral exposure typically produces no acute systemic effects due to minimal absorption. Regarding chronic concerns, in vitro studies have demonstrated genotoxic potential for indigo carmine at high concentrations, including DNA damage and chromosomal aberrations in cell lines such as human fibroblasts and yeast. However, comprehensive reviews conclude no overall genotoxicity concern in vivo, as negative results predominate in bacterial mutagenicity assays and mammalian tests. Long-term rodent studies show no evidence of carcinogenicity, with no tumors observed at doses up to 500 mg/kg body weight per day over 2 years. Certain populations may exhibit heightened sensitivity to indigo carmine. Individuals with have reported , including occupational cases of wheezing and dyspnea following exposure to the dye. Although some studies on mixtures of synthetic colors suggested links to hyperactivity in children, indigo carmine was not included in the key investigation of , and subsequent evaluations found no specific association or causal evidence for behavioral effects from this dye alone. Toxicological assessments establish safe exposure limits for indigo carmine. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) set an (ADI) of 0-5 mg/kg body weight in 1975, based on a (NOAEL) of 500 mg/kg per day from a 2-year dog study, applying a 100-fold factor. The (EFSA) confirmed this ADI in its 2014 re-evaluation, identifying a NOAEL of 500 mg/kg per day from multiple chronic, reproductive, and developmental toxicity studies in rats and dogs, with no adverse effects observed at this level.

Regulatory approvals and limits

In the United States, the (FDA) has approved indigo carmine as the color additive FD&C Blue No. 2 for use in foods, ingested drugs, , and certain devices, with permanent listings established in 1987 for foods and ingested drugs under 21 CFR §74.102 and §74.1102, respectively. This approval requires batch certification to ensure purity and , and it permits general use in foods consistent with current good practices, though specific limitations apply to medical applications such as surgical sutures (not to exceed 1%) and (not to exceed 0.1%). In April 2025, the FDA and U.S. Department of Health and Human Services announced a national initiative to phase out petroleum-based synthetic dyes, including FD&C Blue No. 2, from the supply by the end of 2026 on a voluntary basis, with ongoing industry commitments extending to 2027. In the , indigo carmine is authorized as the E 132 under Regulation (EC) No 1333/2008, with maximum permitted levels (MPLs) ranging from 50 to 500 mg/kg in various food categories such as beverages, , and preserved fruits. The (EFSA) re-evaluated E 132 in 2014 and established an (ADI) of 5 mg/kg body weight (bw) per day, concluding it is safe at or below this level but noting that high-level exposure estimates could exceed the ADI for toddlers and children based on MPL usage. A 2023 follow-up assessment by EFSA confirmed the ADI of 5 mg/kg bw per day and found no safety concerns at reported use levels, with recommendations for refined exposure monitoring in vulnerable populations like children. Internationally, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) has set an ADI for indigotine (indigo carmine) at 0–5 mg/kg bw, originally established in 1975 and reaffirmed in subsequent evaluations, providing a global benchmark for safe intake levels across food applications. In China, indigo carmine is permitted as a synthetic food colorant under National Food Safety Standard GB 2760-2014, with a maximum usage level of 0.1 g/kg (100 mg/kg) in specified foods to ensure compliance with safety thresholds. For medical use, indigo carmine is subject to the (USP) monograph for indigotindisulfonate sodium, which requires a minimum purity of 96.0% and a maximum of 102.0% on the dried basis to guarantee pharmaceutical quality. As an injectable diagnostic agent, it is contraindicated in patients with known to the dye and is not recommended for those with severe renal impairment (eGFR <30 mL/min), due to its primary excretion via renal tubular secretion, which could prolong systemic exposure.

References

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