ロイコマラカイトグリーン

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).

Malachite green, originating in water as a result of its industrial applications or from its illegal use in aquaculture, is metabolically reduced by fish to the persistent colorless metabolite, leucomalachite green. The estimated the mean level for malachite green is 30.7 ug/kg fish muscle (97.5th percentile = 138 ug/kg). Assuming the daily consumption of fish in the UK to be 300 g/person, the daily exposure to the sum of malachite green and leucomalachite green can be calculated to be 9.2 and 41 ug/person at the mean and 97.5th percentile, respectively. For a 60-kg person, this would be equivalent to 0.15 ug/kg body weight per day and 0.69 ug/kg body weight per day, respectively(1).

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from, as of June 21, 2012: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=129-73-7]

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).

/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

Leocomalachite green is a biometabolic product of malachite green. Malachite green in water originates from contamination as a result of its industrial applications or from its illegal use in aquaculture and is efficiently taken up from the water by fish and distributed to all tissues. The rate of excretion of leucomalachite green from fish is dependent on the fat content of the fish, with more leucomalachite green being retained in fatty fish than in lean fish. Therefore, when fish that have been exposed to malachite green reach the consumer, the amount of leucomalachite green present in the fish is expected to be higher than the parent, due to its longer elimination half-life(1).

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).

Leucomalachite green

Group 2B: Possibly carcinogenic to humans

Volume 129: (2022) Gentian Violet, Leucogentian Violet, Malachite Green, Leucomalachite Green, and CI Direct Blue 218

2022 online

2021

Leucomalachite Green

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).

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).

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In a GLP-compliant study, groups of eight male rats (F344/N Nctr BR) (6-7 weeks of age) were given 0, 290, 580 or 1160 mg leucomalachite green (LMG)/kg diet (equivalent to 0, 29, 58 and 116 mg LMG/kg bw per day) for 28 days. Haematology measurements included leukocyte count, erythrocyte count, hemoglobin, hematocrit, mean erythrocyte volume, mean erythrocyte hemoglobin, mean erythrocyte hemoglobin concentration, platelet count, segmented neutrophils, lymphocytes, monocytes, eosinophils and reticulocyte count. Clinical chemistry measurements included total protein and bile acids, blood urea nitrogen, creatinine, ALT, alkaline phosphatase, AST, glucose, cholesterol, triglycerides, GGT, albumin, sorbitol dehydrogenase, creatine kinase, sodium, potassium, chloride, calcium and phosphorus. Male rats fed 1160 mg LMG/kg diet had significantly lower body weights (91-92% of the control group) at weeks 2, 3 and 4. There were also significant decreases in body weights in the 580 mg LMG/kg diet group at weeks 3 and 4 (94% of the control group). The ratio of liver weights to body weights was significantly increased for all three dose groups as compared with the control group. GGT levels were 2.2-fold higher (P < 0.05) and phosphorus levels were slightly increased (10%; P < 0.05) in rats fed 1160 mg LMG/kg diet. In addition, erythrocyte count, haemoglobin and haematocrit levels showed slight (<6%), but significant, decreases from the controls in the 1160 mg/kg diet dose group. Hepatocyte vacuolization, primarily midzonal and centrilobular in location, was seen in seven rats fed 1160 mg LMG/kg diet (P < 0.005), five rats fed 580 mg LMG/kg diet (P < 0.04) and two rats fed 290 mg LMG/kg diet, a significant dose trend (P < 0.0004). Two rats fed 1160 mg LMG/kg diet and two rats fed 580 mg LMG/kg diet had apoptotic follicular epithelial cells in the thyroid gland. Morphological changes consisted of sloughed follicular cells with condensed nuclei located within the follicles. An inflammatory reaction was not present. There was evidence of follicular epithelium regeneration, since even the most severely affected follicles were still lined by viable epithelium. A NOAEL was not established in this study.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In a GLP-compliant study, groups of eight female mice (B6C3F1/Nctr BR (C57BL/6N x C3H/HeN MTV..)) were given leucomalachite green (LMG) (>98% pure) at 0, 290, 580 or 1160 mg/kg diet (equivalent to 0, 43.5, 87 and 174 mg/kg bw per day) for 28 days. Hematology measurements included leukocyte count, erythrocyte count, hemoglobin, hematocrit, mean erythrocyte volume, mean erythrocyte hemoglobin, mean erythrocyte hemoglobin concentration, platelet count, segmented neutrophils, lymphocytes, monocytes, eosinophils and reticulocyte count. Clinical chemistry measurements included total protein and bile acids, blood urea nitrogen, creatinine, ALT and alkaline phosphatase. The female mice fed 1160 mg LMG/kg diet had significantly lower body weights (93% of the control group) at week 4. A marginally significant decrease in body weight (P < 0.01) from the control group was also observed in the female mice fed 580 mg LMG/kg diet at week 4. In addition, there were statistically significant linear dose trends for week 3 (P < 0.02) and week 4 (P < 0.002). All female mice fed 1160 mg LMG/kg diet had scattered dead or degenerate cells in the transitional epithelium of the urinary bladder (P < 0.001). Many of the cells lacked nuclei; when visible, the nuclei were condensed or fragmented, which the authors thought suggested apoptosis. Examination of thin sections revealed that many apparent apoptotic cells were contained within phagocytic vacuoles inside viable epithelial cells. The in situ end labelling technique for detecting deoxyribonucleic acid (DNA) fragmentation showed that the cytoplasm of apparently apoptotic cells was moderately positive for the presence of DNA fragments, and condensed nuclei stained intensely for DNA fragmentation. Individual cell necrosis was not accompanied by inflammatory changes. Similar apoptosis was not seen in transitional epithelium of the bladders of female mice fed 0, 290 or 580 mg LMG/kg diet. The NOAEL was 290 mg LMG/kg diet, equivalent to 43.5 mg LMG/kg bw per day.