Some of the most significant studies on the dye CI 42051 used in bakery products and medicine.

Safety and efficacy of computed tomography-guided dye localization using patent blue V for single lung nodule for video-assisted thoracoscopic surgery: a retrospective study.
Chen JR, Tseng YH, Lin MW, Chen HM, Chen YC, Chen MC, Lee YF, Chen JS, Chang YC.
Ann Transl Med. 2019 Jan;7(2):28. doi: 10.21037/atm.2019.01.27.

Novel use of Patent Blue V dye to facilitate repair of lymph leak after groin debridement.
Hariswamy S, Lambrakis P.
ANZ J Surg. 2018 Apr;88(4):386-387. doi: 10.1111/ans.14425

Antiplasmodial activities of dyes against Plasmodium falciparum asexual and sexual stages: Contrasted uptakes of triarylmethanes Brilliant green, Green S (E142), and Patent Blue V (E131) by erythrocytes.
Leba LJ, Popovici J, Estevez Y, Pelleau S, Legrand E, Musset L, Duplais C.
Int J Parasitol Drugs Drug Resist. 2017 Dec;7(3):314-320. doi: 10.1016/j.ijpddr.2017.07.002

A prospective randomized trial comparing patent blue and methylene blue for the detection of the sentinel lymph node in breast cancer patients.
Paulinelli RR, Freitas-Junior R, Rahal RM, Oliveira LF, Vilela MH, Moreira MA, Alves KL, Peleja MB, Resende TC.
Rev Assoc Med Bras (1992). 2017 Feb;63(2):118-123. doi: 10.1590/1806-9282.63.02.118.

A Case of Anaphylaxis to Patent Blue in a Patient with Sentinel Lymph Node Excision.
Aurich S, Seitz AT, Tomm J, Simon JC, Treudler R.
Iran J Allergy Asthma Immunol. 2016 Dec;15(6):547-550

Blue dye for identification of sentinel nodes in breast cancer and malignant melanoma: a systematic review and meta-analysis.
Peek MC, Charalampoudis P, Anninga B, Baker R, Douek M.
Future Oncol. 2017 Feb;13(5):455-467. doi: 10.2217/fon-2016-0255

Patent blue V and indocyanine green for fluorescence microimaging of human peritoneal carcinomatosis using probe-based confocal laser endomicroscopy.
Abbaci M, Dartigues P, De Leeuw F, Soufan R, Fabre M, Laplace-Builhé C.
Surg Endosc. 2016 Dec;30(12):5255-5265

The Nordic SentiMag trial: a comparison of super paramagnetic iron oxide (SPIO) nanoparticles versus Tc(99) and patent blue in the detection of sentinel node (SN) in patients with breast cancer and a meta-analysis of earlier studies.
Karakatsanis A, Christiansen PM, Fischer L, Hedin C, Pistioli L, Sund M, Rasmussen NR, Jørnsgård H, Tegnelius D, Eriksson S, Daskalakis K, Wärnberg F, Markopoulos CJ, Bergkvist L.
Breast Cancer Res Treat. 2016 Jun;157(2):281-294. doi: 10.1007/s10549-016-3809-9

Anaphylactic reaction to patent blue V used in preoperative computed tomography-guided dye localization of small lung nodules.
Wu TT, Chang YC, Lee JM, Hung MH.
J Formos Med Assoc. 2016 Apr;115(4):288-9. doi: 10.1016/j.jfma.2015.04.003

The effects of Patent Blue dye on peripheral and cerebral oxyhaemoglobin saturations.
Ishiyama T, Kotoda M, Asano N, Ikemoto K, Mitsui K, Sato H, Matsukawa T, Sessler DI.
Anaesthesia. 2015 Apr;70(4):429-33. doi: 10.1111/anae.12932. Epub 2014 Nov 10.

CI 42051 is a chemical compound is a synthetic dye, triphenylmethane. Triphenylmethane is a dark blue hydrocarbon. It is also known as Patent blue V, Acid blue 3. 

Raw Materials Typically Used in the Production of Patent Blue V (E131) and Their Functions

• Aniline. A primary ingredient used in the synthesis of many dyes, including Patent Blue V. It acts as a base molecule that is chemically modified to produce the dye.
• Sulfuric Acid. Often used in the dye-making process as a sulfonating agent to introduce sulfonic acid groups into the molecule, enhancing the dye's water solubility.
• Formaldehyde. Used in the chemical reaction to help in the polymerization process or as a stabilizing agent.
• Other Chemical Reagents. Various other reagents and catalysts may be involved in the synthesis process to facilitate the formation of the dye and to achieve the desired chemical structure.

Industrial Production Process

• Chemical Synthesis. Patent Blue V is produced through a complex chemical synthesis process, which involves the reaction of aniline with other chemicals, including sulfuric acid and formaldehyde, under controlled conditions.
• Purification. After synthesis, the dye is purified to remove impurities and ensure the quality of the color.
• Quality Control. Each batch of Patent Blue V undergoes quality testing to ensure its compliance with safety and purity standards.

Form and Color

Patent Blue V typically appears as a fine powder with an intense blue color

What it is used for and where

Food

It is labelled with the number E131 in the list of European colour additives.

Cosmetics

Blue dye.

Medical

Medical imaging in healthcare monitoring.

Safety

Two of EFSA’s Scientific Panels have both concluded that the colour Patent Blue V (E 131) is not a safety concern for people or animals when used as a food or feed additive at current levels of use. According to EU food and feed legislation, EFSA is required to operate under different regulatory frameworks with separate data requirements. 

From a genotoxic point of view, no effect has also been detected.

However, several studies have found cases of allergy to this dye (1).

Patent blue V studies

Molecular Formula: C₂₇H₃₁N₂O₇S₂Na (sodium salt)

CAS: 20262-76-4

EC Number: 243-654-4

Molecular Formula: C₂₇H₃₁N₂O₇S₂Ca (calcium salt)

CAS: 3536-49-0

Molecular Weight: 1159.422 g/mol

UNII: 8QE473DV1Z

Synonyms:

• Acid blue 3
• New Patent Blue A-CE Extra
• New Patent Blue Extra Pure A
• Acidal Carmine V
• E131
• Mitsui Acid Pure Blue VX
• Dai-ei Acid Pure Blue VX
• Alphazurine 2 G (C.I. 42051)
• Merantine Blue V
• Food Blue 5
• Solar Pure Blue VX
• Schultz No. 826
• Blue ZN 3
• Patent Blue V and L
• Carmine Blue V
• L-Blau 3 [German]
• C.I. Acid Blue 3
• C.I. Food Blue 5

References_____________________________________________________________________

(1) Vidya R, Athwal R, Huissoon AP, Baretto RL, Thirumala Krishna M. Diagnostic application of patent blue V in sentinel lymph node biopsy for breast cancer - Is it time for a change? Indian J Cancer. 2019 Jul-Sep;56(3):269-270. doi: 10.4103/ijc.IJC_139_18. PMID: 31389393.

Abstract. Sentinel lymph node biopsy (SLNB) was introduced in the 1990s, as a minimally invasive procedure for staging the axilla with less morbidity to the traditional axillary lymph node dissection and is now standard management of the axilla in the early breast cancer. SLNB using the combined technique of blue dye and radioisotope is currently the recommended method for lymphatic mapping, and studies have shown high identification rates (IR) (>95%) and low false-negative rates (FNR) 5-10%. However, there are several reports raising awareness regarding patent blue V dye-induced peri-operative anaphylaxis. The main aim of this article is to highlight the emergence of patent blue dye as a new allergen and present evidence regarding the utility of alternative safer methods of evaluation of early breast cancer without compromising IR.

Misir Šitum S, Korečić Zrinjščak I, Pečvarac M, Šoštar A, Žaja A, Tot T. Case report: Atypical anaphylactic reaction to Patent Blue V dye during breast cancer surgery. Front Oncol. 2022 Sep 16;12:979393. doi: 10.3389/fonc.2022.979393.

Costa D, Mendonça M, Lopes M, Fernandes AL, Nunes S, Müller S. Anafilaxia por corante azul patente V: relato de caso e revisão da literatura [Patent blue V dye anaphylaxis: a case report and literature review]. Braz J Anesthesiol. 2020 Nov-Dec;70(6):662-666. doi: 10.1016/j.bjan.2020.05.005.

 CI 42051 is a blue dye that is identified with a wide variety of synonyms.

 It is used, in various percentages, in food, medical, cosmetics (in the preparation of creams, detergents, shampoos, etc.).

 In the medical field, it serves as a vital lymphatic dye to be injected in a 2.5% solution in order to improve the detection rate of any sentinel lymph nodes (1).

 Patent blue V (PBV) and its isomer isosulfan blue (IB) are obtained from patent blue or sulfan blue dye. Both PBV and IB show lymphatic tropism and are therefore used in sentinel lymph node biopsies (SLNBs). European groups use PBV while Americans use IB; the 2 dyes have high cross-reactivity. The prevalence of allergic reactions to PBV is 0.34% to 0.5%, but one UK study reported a prevalence of 6% for intraoperative anaphylaxis linked to PBV. The reported prevalence of allergic reactions to IB varies between 1% and 2% (2).

 In the food sector it has been authorized by the European Directive 78/25 / EEC dated 12/12/1977 with the name of Patent Blu V

Two of EFSA’s Scientific Panels have both concluded that the colour Patent Blue V (E 131) is not a safety concern for people or animals when used as a food or feed additive at current levels of use. According to EU food and feed legislation, EFSA is required to operate under different regulatory frameworks with separate data requirements. (3).

 As for the food safety of this dye you can deepen with these texts (4).

 Molecular formula C₅₄H₆₂CaN₄O₁₄S₄

 Molecular weight: 1159.43

 CAS: 3536-49-0

 Synonyms :

E131 in the food sector
Acid Blue 3
Acidal carmine V
Blue Patent V in the medical field
Patent blue V
Cosmetic green blue R25396
C-Blau 20
Blue disulfine
Erio brilliant blue V
L-Blau 3
Patentblau
Pontacy brilliant blue

 and : Blue ZN 3, sulfan blue, sulphan blue, disulphine blue, disulfine blue, Carmine Blue V, Acidal Carmine V, Merantine Blue V, Alphazurine 2 G, NSC 5010, NSC 75430, EINECS 222-573-8, C.I. Food Blue 5, C.I. Acid Blue 3, Mitsui Acid Pure Blue VX, m-Hydroxytetraethyldiaminotriphenylcarbinol anhydride disulfonic acid calcium salt, Bis(hydrogen (4-(4-(diethylamino)-5'-hydroxy-2',4'-disulphonatobenzhydrylidene)cyclohexa-2,5-dien-1-ylidene)diethylammonium), calcium salt, Ethanaminium, N-(4-((4-(diethylamino)phenyl)(5-hydroxy-2,4-disulfophenyl)methyl- ene)-2,5-cyclohexadien-1-ylidene)-N-ethyl-, hydroxide, inner salt, calcium salt (2:1), N-(4-((4-(Diethylamino)phenyl)(5-hydroxy-2,4-disulfophenyl)methyl- ene)-2,5-cyclohexadien-1-ylidene)-N-ethylethanaminium, hydroxide, inner salt, calcium salt (2:1), Ethanaminium, N-(4-((4-(diethylamino)phenyl)(5-hydroxy-2,4-disulfophenyl)methylene)-2,5-cyclohexadien-1-ylidene)-N-ethyl-, inner salt, calcium salt (2:1), Ethanaminium, N-(4-((4-(diethylamino)phenyl)(5-hydroxy-2,4-disulfophenyl)methylene)-2,5-cyclohexadien-1-ylidene)-N-ethyl-, hydroxide, inner salt, calcium salt (2:1), calcium bis(4-{[4-(diethylamino)phenyl][4-(diethyliminio)cyclohexa-2,5-dien-1-ylidene]methyl}-6-hydroxybenzene-1,3-disulfonate), sodium 4-((4-(diethylamino)phenyl)(4-(diethyliminio)cyclohexa-2,5-dien-1-ylidene)methyl)benzene-1,3-disulphonate, ethanaminium, n-(4-((4-(diethylamino)phenyl)(2,4-disulfophenyl)methylene)-2,5-cyclohexadien-1-ylidene)-n-ethyl-, hydroxide, inner salt, sodium salt

References_____________________________

 (1) Preoperative lymphoscintigraphy and sentinel lymph node biopsy in papillary thyroid cancer. A pilot study.

Catarci M, Zaraca F, Angeloni R, Mancini B, de Filippo MG, Massa R, Carboni M, Pasquini G. J Surg Oncol. 2001 May;77(1):21-4; discussion 25.

The Nordic SentiMag trial: a comparison of super paramagnetic iron oxide (SPIO) nanoparticles versus Tc(99) and patent blue in the detection of sentinel node (SN) in patients with breast cancer and a meta-analysis of earlier studies.

Karakatsanis A, Christiansen PM, Fischer L, Hedin C, Pistioli L, Sund M, Rasmussen NR, Jørnsgård H, Tegnelius D, Eriksson S, Daskalakis K, Wärnberg F, Markopoulos CJ, Bergkvist L.

Breast Cancer Res Treat. 2016 Jun;157(2):281-294. doi: 10.1007/s10549-016-3809-9. Epub 2016 Apr 27.

Sentinel lymph-node biopsy in breast cancer: five years' experience.

Gioffrè Florio MA, Famà F, Gullo G, Pollicino A, Scarfò P.  Chir Ital. 2004 Jan-Feb;56(1):107-12. Italian.

(2) Allergy to Blue Dye.

Martín-Lázaro J, Núñez-Orjales R, Battikhi-Precedo N, López-Freire S, Carballada-González F.

J Investig Allergol Clin Immunol. 2016;26(6):381-383. doi: 10.18176/jiaci.0101

(3) Scientists at EFSA further strengthen co-ordination of food and feed additive evaluations- EFSA 1 March 2013

(4) Sax's dangerous properties of industrial materials pg 58 and pg 935

Richard J. Lewis, Newton Irving Sax
John Wiley & Sons, 2000 - 1900 pg

Human Toxicology of Chemical Mixtures - Harold Zeliger - pg.138