Leucomalachite green

330.47

330.47

204-961-9

8U61G37Z20

36379

DTXSID7031531

Off-white to light-brown powder|Needles or leaflets from alcohol, benzene

2921590090

6.5

5.72 (est)

White to light brown, light green or light blue Powder

1.1±0.1 g/cm3

92 °C

475.4±45.0 °C at 760 mmHg

214.6±16.5 °C

1.621

soluble in water (<0.1 mg/ml), chloroform, benzene, ethyl ether, ethanol and toluene.Solubilities (mg/mL): 30 ethyleneglycol monomethyl ether; 4 ethanol

1.92X10-7 mm Hg at 25 deg C (est)

Henry's Law constant = 9.79X10-9 atm-cu m/mol at 25 °C (est)

pKa = 5.46 (amine) (est)

199.77 Ų [M+H]+

Hydroxyl radical reaction rate constant = 2.07X10-10 cu cm/molec-sec at 25 °C (est)

UN30779/PG3

40-50/53-22-36/37/38

36/37-61-60-36/37/39-27-26

CY1203055

Xn,N,Xi

P201-P308 + P313

H341-H351

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.

|Warning|H341: Suspected of causing genetic defects [Warning Germ cell mutagenicity]|P201, P202, P281, P308+P313, P405, and P501|Danger|H302 (96.08%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P273, P280, P301+P312, P302+P352, P304+P312, P304+P340, P311, P312, P321, P322, P330, P332+P313, P361, P362, P363, P391, P403+P233, P405, and P501|Aggregated GHS information provided by 51 companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|P201, P202, P260, P264, P270, P281, P308+P313, P314, P405, and P501

Groups of 48 female /B6C3F1/ mice were fed diets containing 0, 91, 204, or 408 ppm leucomalachite green for 2 years (equivalent to average daily doses of approximately 0, 13, 31, and 63 mg leucomalachite green/kg body weight). Survival of exposed groups was similar to that of the controls. Mean body weights were generally similar to those of the controls. Feed consumption by exposed groups was generally similar to that by the controls. Relative kidney weights were significantly decreased in all dose groups. The incidences of hepatocellular adenoma or carcinoma (combined) occurred with a positive trend and the incidence was significantly increased in 408 ppm mice. The incidences of hepatocellular adenoma were increased (not statistically significant) in exposed mice. ... There was some evidence of carcinogenic activity of leucomalachite green in female B6C3F1 mice based on an increase in hepatocellular adenoma or carcinoma (combined). ... Exposure to leucomalachite green in feed resulted in nonneoplastic lesions in the ... urinary bladder of female mice.|Groups of 48 male and female /F344/N/ rats were fed diets containing 0, 91, 272, or 543 ppm leucomalachite green in feed for 2 years (equivalent to average daily doses of approximately 0, 5, 15, and 30 mg leucomalachite green/kg body weight to males and 0, 6, 17, and 35 mg/kg body weight to females). Survival of 272 ppm males was greater than that of the controls. Mean body weights of 543 ppm males and females and 272 ppm females were less than those of the controls throughout the study; mean body weights of 272 ppm males and 91 ppm females were less than those of the controls during year 2 of the study. Feed consumption by 543 ppm males and females was intermittently less than that by the controls throughout the study; feed consumption by 272 ppm females was intermittently less during year 2 of the study. Liver weights were significantly increased for 272 and 543 ppm males; relative liver weights were significantly increased for 272 and 543 ppm females. Relative thyroid gland weights of 543 ppm males and females were significantly increased. Hepatocellular adenomas were minimally increased (not statistically significant) in female rats exposed to 91 or 543 ppm leucomalachite green, with the incidence exceeding the historical control range. Nonneoplastic liver lesions including eosinophilic focus, cystic degeneration, and cytoplasmic vacuolization were generally significantly increased in the exposed groups of male and female rats. Thyroid gland follicular cell adenomas or carcinomas (combined) and cysts were observed in exposed males and females. The increases were minimal and not statistically significant; however, the increases may be biologically significant due to the rarity of the neoplasm and related nonneoplastic changes. Testicular interstitial cell adenoma occurred with a positive trend in male rats, and the incidence was significantly increased in the 543 ppm group. The broad range of incidences in the historical control data and the uncertainty of the relationship between pituitary gland neoplasms and testicular adenomas may confound this result. The incidences of mononuclear cell leukemia were significantly decreased in exposed rats. The incidences of pituitary gland adenoma were significantly decreased in exposed male rats. Under the conditions of this 2-year feed study, there was equivocal evidence of carcinogenic activity of leucomalachite green in male F344/N rats based on an increase in interstitial cell adenoma of the testes and the occurrence of thyroid gland follicular cell adenoma or carcinoma (combined) in exposed rats. There was equivocal evidence of carcinogenic activity of leucomalachite green in female F344/N rats based on a marginally increased incidence of hepatocellular adenoma and the occurrence of thyroid gland follicular cell adenoma or carcinoma (combined) in exposed rats. ... Exposure to leucomalachite green in feed resulted in nonneoplastic lesions in the thyroid gland and liver of male and female rats ... .

Leucomalachite green's production and use as a dye precursor and biochemical lab reagent(1) may result in its release to the environment through various waste streams(SRC). The dye must be protected from light and the atmosphere to prevent oxidation to the malachite green carbinol base(1).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 9.8X10+4(SRC), determined from a structure estimation method(2), indicates that leucomalachite green is expected to be immobile in soil(SRC). The estimated pKa of leucomalachite green is 5.46(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of the neutral species from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 9.8X10-9 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Leucomalachite green is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.9X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(6). Biodegradation data in soil were not available(SRC, 2012).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 9.8X10+4(SRC), determined from a structure estimation method(2), indicates that leucomalachite green is expected to adsorb to suspended solids and sediment(SRC). Volatilization of the neutral species from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 9.8X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). The estimated pKa of 5.72(5) indicates leucomalachite green will exist partially in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(6), an estimated BCF of 2800(SRC), from an estimated log Kow of 5.72(7) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is very high, provided the compound is not metabolized by the organism(SRC). Biodegradation data in water were not available(SRC, 2012).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), leucomalachite green, which has an estimated vapor pressure of 1.9X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase leucomalachite green is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 0.6 hours(SRC), calculated from its rate constant of 2.1X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase leucomalachite green may be removed from the air by wet or dry deposition(SRC). Leucomalachite green contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of leucomalachite green with photochemically-produced hydroxyl radicals has been estimated as 2.1X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 0.6 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Leucomalachite green does not contain chromophores that absorb at wavelengths >290 nm(2) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 2800 was calculated in fish for leucomalachite green(SRC), using an estimated log Kow of 5.72(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is very high(SRC), provided the compound is not metabolized by the organism(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of leucomalachite green can be estimated to be 9.8X10+4(SRC). According to a classification scheme(2), this estimated Koc value suggests that leucomalachite green is expected to be immobile in soil. The estimated pKa of leucomalachite green is 5.46(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

The Henry's Law constant for the neutral species of leucomalachite green is estimated as 9.8X10-9 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that leucomalachite green is expected to be essentially nonvolatile from water and moist soil surfaces(2). The estimated pKa of 5.72(3) indicates leucomalachite green will exist partially in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(SRC). Leucomalachite green is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.9X10-7 mm Hg(SRC), determined from a fragment constant method(4).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 28 workers (none of these were female) were potentially exposed to leucomalachite green in the US(1). The greatest potential for dermal and inhalation exposure to leucomalachite green is expected at the manufacturing site and to a lesser extent during activities at consumer sites(SRC).

In liver extracts from rats treated with leucomalachite green (LMG), primarily protonated LMG, protonated demethylated derivatives and the molecular ions of malachite green N-oxide and demethylated N-oxide derivatives were seen. A small, but measurable, amount of malachite green was also found. A dose-related increase in LMG and metabolites was observed in both rat and mouse liver extracts.|... The reduction of malachite green (MG) to leucomalachite green (LMG) by intestinal bacteria from humans, rats, mice and rhesus monkeys and 14 pure cultures of anaerobic bacteria representative of those found in the human gastrointestinal tract. The bacterial cultures were incubated with 300 ug of MG in 5 mL of brain-heart infusion broth for 24-48 hr under anaerobic conditions. Virtually all of the MG was converted to its LMG derivative by the intestinal microflora. The pure bacterial cultures converted 7.3-99.3% of the MG to LMG. These results indicate the importance of the gastrointestinal tract microflora in the conversion of MG to LMG.|Intestinal microfloras from human, rat, mouse, and monkey fecal samples and 14 pure cultures of anaerobic bacteria representative of those found in the human gastrointestinal tract metabolized the triphenylmethane dye malachite green to leucomalachite green. The reduction of malachite green to the leuco derivative suggests that intestinal microflora could play an important role in the metabolic activation of the triphenylmethane dye to a potential carcinogen.|Malachite green (MG) is still illegally used as a fungicide in aquaculture. In fish it is absorbed and metabolised to its major reduced metabolite, leucomalachite green (LMG). This latter represents the main residue found in fish tissues and may persist for several months.

The half-life of LMG residence in trout muscle may be as long as 40 days.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/ALTERNATIVE and IN VITRO TESTS/ ... Since malachite green (MG), suspected to act as a tumor promoter in vitro and in vivo, might be also present as a residue in fish, the present study was undertaken to ascertain the in vitro toxicity of both compounds in two human tumour cell lines (Caco-2 and HEp-2). After 24 hr incubation with MG, significant decreases of cell viability, measured by neutral red uptake (NRU) or total protein content (TPC) as well as proliferation capability (colony-forming ability, CFA) were noticed in HEp-2 cells; the mean IC(50) value was about 2 uM. As regards the differentiated Caco-2 cells, MG caused a dose-related significant cytotoxicity, measured either by MTT test, the LDH leakage or NRU, with a mean IC(50) value of about 15 uM. By contrast, LMG disclosed, in both cell lines, a lower cytotoxicity compared to MG. These results also show that HEp-2 cells are more sensitive than intestinal cells to the toxic action of both compounds

4,4'-benzylidenebis(N,N-dimethylaniline)

Benzenamine, 4,4'-(phenylmethylene)bis[N,N-dimethyl-: ACTIVE|Malachite green (MG), a triphenylmethane dye, has been applied extensively to fish worldwide in aquaculture operations. It has been administered as a therapeutic agent against common external parasites, as well as used for some skin and gill diseases. MG is environmentally persistent and is toxic to a wide range of aquatic and terrestrial animals. MG undergoes a conversion to the reduced leuco form in fish tissue when absorbed through the skin. A metabolite, leucomalachite green (LMG), accumulates in the muscle tissue of exposed fish for a relatively long time with a half-life of about 40 days. ... MG and its metabolite LMG are multi-organ toxins. The toxicity of the compound increases with increased time and concentration of exposure.|... Must be protected from light and the atmosphere to prevent oxidation to the Malachite Green Carbinol base|Colorless precursor of Malachite Green|A class of water-insoluble dyes that can be easily reduced, i.e. vatted to a water soluble and usually colorless leuco form in which they can readily impregnate fibers. Subesquent oxidation then produces the insoluble colored form that is remarkably fast to washing, light, and chemicals ... For cotton, wool, and cellulose acetate /Vat dye/

The chromatic and leuco forms of malachite green and crystal violet were readily separated and detected by a sensitive and selective high-performance liquid chromatographic procedure. The chromatic and leuco forms of the dyes were separated within 11 min on a C18 column with a mobile phase of 0.05 M sodium acetate and 0.05 M acetic acid in water (19%) and methanol (81%). A reaction chamber, containing 10% PbO2 in Celite 545, was placed between the column and the spectrophotometric detector to oxidize the leuco forms of the dyes to their chromatic forms. Chromatic and leuco malachite green were quantified by their absorbance at 618 nm; and chromatic and leuco Crystal Violet by their absorbance at 588 nm. Detection limits for chromatic and leuco forms of both dyes ranged from 0.12 to 0.28 ng. A linear range of 1 to 100 ng was established for both forms of the dyes.

... A simplified method /is presented/ for the determination of LMG /leucomalachite green/ and MG /malachite green/ in salmon that reduces sample size, solvent volume, minimizes sample preparation, and introduces an in-situ oxidation of LMG to MG with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) to eliminate the need for post-column lead oxide oxidation.8 Visible absorbance at 618 nm is used to determine a single MG chromatographic peak that results from either the presence of LMG or MG in the salmon. This method results in the quantitative determination of LMG and MG in salmon with a residue detection limit of 1.0 ng/g.|To determine residues of malachite green (MG) and its metabolite, leucomalachite green (LMG), in catfish tissue, analytes are extracted with acetonitrile-buffer and the extract is partitioned into methylene chloride. Final cleanup and isolation are performed on neutral alumina solid-phase extraction (SPE) and propylsulfonic acid cation-exchange SPE columns before analysis by liquid chromatography with visible detection. PbO2 postcolumn oxidation is performed by isocratic elution with a buffered mobile phase from a cyano column. Recoveries and relative standard deviations (RSDs) from fortified catfish tissues were 72.9% (RSD, 1.92%; 23 ppb), 75.5% (RSD, 6.85%; 11 ppb), and 69.6% (RSD, 6.93%; 5.7 ppb) for MG and 87.4% (RSD, 2.92%; 21 ppb), 88.1% (RSD, 5.94%; 10 ppb), and 82.6% (RSD, 11.5%; 5.3 ppb) for LMG. The method was applied to MG-incurred catfish at depuration times of 0, 2, 4, 8, and 24 h. Average levels of residual MG and LMG in the 24 h depuration catfish tissue were 73.4 and 289 ppb, respectively.|A gas chromatographic/mass spectrometric (GC) method was developed to confirm the presence of leucomalachite green (LMG), a metabolite of the triphenylmethane dye malachite green (MG), in catfish tissue. Residues were isolated according to a previously described liquid chromatographic (LC)/VIS spectrometric analysis of MG and LMG in fish. In our isolation procedure, analytes are extracted from tissue with acetonitrile-buffer, partitioned into CH2Cl2, and applied to neutral alumina and propylsulfonic acid solid-phase extraction cartridges. Before GC/MS analysis, extracts prepared for the LC determinative method are eluted from a cyano solid-phase extraction cartridge, extracted into organic solvent, and concentrated for GC/MS analysis. Selected ion monitoring was performed by using 5 diagnostic ions (m/z 330, 329, 253, 21 0, and 165) of LMG ...