CI 61565, also known as Solvent Green 3,D & C Green No. 6 is a synthetic dye from the anthraquinone family. It is primarily used for coloring a wide range of industrial and cosmetic products, including soaps, detergents, waxes, and some cosmetics. Its vibrant green hue is utilized to enhance the visual appeal of products. However, its use is restricted in certain sectors due to safety concerns.

Chemical Composition and Structure

It is an organic compound with the chemical structure 1,4-di-p-toluidinoanthraquinone. This structure classifies it as a substituted anthraquinone, with amino and methyl groups contributing to its intense green color. Anthraquinones are known for their high stability and lightfastness, making them suitable for coloring applications.

Physical Properties

It appears as a crystalline green powder. It is soluble in organic solvents but insoluble in water. Due to its chemical stability, it retains its color even under harsh conditions such as high temperatures and light exposure.

Chemical Name

1,4-bis(4-methylanilino)anthracene-9,10-dione

Production Process

CI 61565 is synthesized through complex chemical processes involving the reaction of anthraquinone with amino and methyl compounds. The production requires precise control of conditions to achieve the desired purity and stability of the dye.

• Preparation of reagents. The main raw materials include phthalic anhydride, benzene, and concentrated sulfuric acid.
• Synthesis of anthraquinone intermediate. The production begins with the condensation of phthalic anhydride with benzene in the presence of concentrated sulfuric acid, forming the anthraquinone intermediate.
• Substitution. The anthraquinone is further treated with specific reagents to introduce functional groups that impart the desired color. This may include sulfonation, nitration, or other substitution reactions.
• Oxidation. The functionalized structure undergoes an oxidation reaction to complete the formation of the anthraquinone chromophore, which is responsible for the coloring properties of CI 61565.
• Purification. The crude product is purified using techniques such as crystallization, filtration, and chromatography to remove impurities and achieve a high-purity colorant.
• Stabilization. The purified product is stabilized to ensure its stability during transportation and storage, preventing degradation and oxidation.
• Quality control. The CI 61565 undergoes rigorous quality testing to ensure it meets standards for purity, color intensity, and safety. These tests include chemical analysis, spectroscopy, and microbiological testing.

Applications

• Cosmetic Industry: Used in some cosmetics, skincare products, and detergents to provide an intense green color.

• Soaps and Detergents: Applied in the coloring of solid and liquid soaps, cleaning agents, and personal care products.

• Waxes and Industrial Products: Also employed for coloring waxes, plastics, and other industrial products.

Cosmetic safety

Restricted cosmetic ingredient as  IV/91 (CI 61565) II/1364 (Solvent Green 3; CI 61565) when used as a substance in hair dye products. a Relevant Item in the Annexes of the European Cosmetics Regulation 1223/2009. Substance or ingredient reported:

• 1,4-bis(p-Tolylamino)anthraquinone

Cosmetics - INCI Functions

Colorant. This ingredient has the function of colouring the solution in which it is inserted in a temporary, semi-permanent or permanent manner, either alone or in the presence of the complementary components added for colouring.

Safety

 It’s forbidden to use in hair coloring products.

Safety in Use
The use of CI 61565 is subject to strict regulations in some countries due to concerns regarding its safety. While approved in certain applications, its use in cosmetic products is limited in some regions due to potential toxicity risks.

Allergic Reactions
Allergic reactions are rare but possible. Some individuals, especially those with sensitive skin, may experience irritation or allergic reactions, particularly if used in high concentrations or in products with prolonged skin contact.

Toxicity and Carcinogenicity
There are concerns about the potential toxicity and carcinogenicity of CI 61565. Some studies suggest that prolonged exposure or use in high concentrations may have harmful health effects. As a result, its use is regulated or restricted in various countries, particularly in products intended for personal use.

Environmental Considerations
As a synthetic dye, it can pose environmental risks if not disposed of properly. It can accumulate in aquatic ecosystems and may be toxic to marine life. The biodegradability of the dye is limited.

Regulatory Status
It is regulated in various countries. In some regions,

its use is allowed only in certain industrial or non-skin-contact cosmetic applications, while in other areas it is subject to stricter restrictions.

Molecular Formula    C₂₈H₂₂N₂O₂

Molecular Weight  418.5 g/mol

CAS   128-80-3

EC number 204-909-5

UNII 4QP5U84YF7

DTXSID9044376

Synonyms: 

Solvent Green 3.

D & C GREEN NO. 6

DC GREEN NO. 6

Quinizarin Green SS

Waxoline Green G

Arlosol Green B

References__________________________________________________________________________

Sun JD, Henderson RF, Marshall TC, Cheng YS, Dutcher JS, Pickrell JA, Mauderly JL, Hahn FF, Banas DA, Seiler FA, et al. The inhalation toxicity of two commercial dyes: solvent yellow 33 and solvent green 3. Fundam Appl Toxicol. 1987 Apr;8(3):358-71. doi: 10.1016/0272-0590(87)90085-6. 

Abstract. The quinoline dye 2-(2'-quinolyl)-1,3-indandione or Solvent Yellow 33 (SY) and the anthraquinone dye 1,4-di-p-toluidinoanthraquinone or Solvent Green 3 (SG) are used in many manufactured products including military smoke grenades. During manufacturing, SY or a combination of both SY and SG can be released into the air, exposing factory workers by inhalation to these dye compounds. The potential inhalation toxicity of these compounds was tested by exposing F344/N rats to different concentrations of SY or SY/SG dye mixture (30:70 w/w) for 6 hr/day, 5 days/week for 4 or 13 weeks. In the 4-week studies, rats were exposed to SY aerosols at average concentrations of 10 +/- 5, 51 +/- 10, or 230 +/- 30 mg/m3 (means +/- SD) or SY/SG aerosols at average concentrations of 11 +/- 5, 49 +/- 11, or 210 +/- 50 mg/m3 (means +/- SD). Rats exposed to the highest concentration of SY or SY/SG had body weights that were approximately 8% or 7% less, respectively, than their controls after exposure. Rats exposed to the highest concentration of SY/SG for 4 weeks also had reduced pulmonary gas exchange efficiency, airflow obstruction, mild pulmonary inflammation, slight Type II pulmonary epithelial cell hyperplasia, and proliferation of vacuolated alveolar macrophages. In the 13-week studies, rats were exposed to SY aerosols at average concentrations of 1.0 +/- 0.2, 10.8 +/- 1.8, or 100 +/- 17 mg/m3 (means +/- SD) or SY/SG aerosols at average concentrations of 1.1 +/- 0.5, 10.2 +/- 3.1, or 101 +/- 23 mg/m3 (means +/- SD). Animals exposed to the highest concentration of SY or SY/SG for 13 weeks had body weights that were approximately 5 or 9% less, respectively, than their controls after exposure and had accumulation of vacuolated alveolar macrophages in lungs. Rats exposed to the highest concentration of SY/SG dye mixture for 13 weeks also had indications of mild pulmonary inflammation and slight Type II pulmonary epithelial cell hyperplasia. Very little SY was found in lungs after any exposures, indicating its clearance from lungs was at a rapid rate. However, significant amounts of the SG component of the SY/SG mixture were detected in lungs after each exposure. Lung clearance half-times of SG from the 13-week exposure were estimated to be approximately 280 days. In summary, neither test material appeared to be highly toxic following inhalation. However, the slightly higher toxicity observed for SY/SG over SY alone is probably related to the longer lung retention of the SG component of the dye mixture.

Iwanaga K, Kushibiki T, Miyazaki M, Kakemi M. Disposition of lipid-based formulation in the intestinal tract affects the absorption of poorly water-soluble drugs. Biol Pharm Bull. 2006 Mar;29(3):508-12. doi: 10.1248/bpb.29.508. 

Abstract. Solvent Green 3 (SG), a model poorly water-soluble compound, was orally administered to rats with soybean oil emulsion or the Self-microemulsifying drug delivery system (SMEDDS) composed of Gelucire44/14. The bioavailability of SG after oral administration with SMEDDS was 1.7-fold higher than that with soybean oil emulsion. The intestinal absorption of lipid-based formulations themselves was evaluated by the in situ closed loop method. The effect of lipase and bile salt on their absorption was also evaluated. SMEDDS itself was rapidly absorbed in the intestine even in the absence of lipase and bile salt, and the absorption was increased by the addition of lipase and bile salt. On the other hand, no soybean oil emulsion was absorbed in the absence of lipase and bile salt. However, mixed micelle prepared from emulsion by incubating soybean oil emulsion with lipase and bile salt was rapidly absorbed through the intestine. Without lipase and bile salt, SG was not absorbed after administration with soybean oil emulsion. Therefore, we concluded that the degradation of soybean oil emulsion was needed for SG to be absorbed through the intestine. Furthermore, we investigated the intestinal absorption of SG after oral administration to rats whose chylomicron synthesis were inhibited by pretreatment with colchicine. Colchicine completely inhibited the intestinal absorption of SG after administration with each lipid-based formulation, suggesting that SG was absorbed from the intestine via a lymphatic route. Absorption of the dosage formulation should be paid attention when poorly water-soluble drugs are orally administered with lipid-based formulation.