Chronic Toxicity and Carcinogenicity Studies of Gentian Violet in Mice

Abstract

9 12. Gentian violet is a dye belonging to a chemical class known as the di-and triaminophenylmethanes. Although it has been used for many years for the control of fungal and intestinal parasites, for various uses in veterinary medicine, and as an additive to the feed of chickens to inhibit propagation of mold and fungus, very few long-term toxicity data are available. A life span dosing study of gentian violet in the diet of 720 males and 720 females of R6C3Fi mice (C57BL/6 X C3H) at dose levels of 0, 100,300, and 600 ppm was done to determine its toxicity and carcinogenicity. Sacrifices were conducted afler 12, 18, and 24 months of continuous dosing. There was no effect on food consumption or body weight gain; however, a dose effect was noted for mortality rates. Mortality (adjusted for sacrifices) in the controls of both sexes was less than 15% at 24 months, but was approximately 64% in the females and 23% in the males given the high dose. Females appeared to be more susceptible than males. A positive dose response for hepatocellular carcinoma was noted in males at 24 months and in females at 18 and 24 months. Statistical tests for dose-related trends with respect to (1) mortality due to liver neoplasms, (2) prevalence of liver neoplasms, and (3) time to onset of liver neoplasms showed positive trends in both males and females. Other dose-related toxicological responses, particularly in the female mice, included erythropoiesis in the spleen, atrophy of the ovaries, adenoma of the Harderian gland, and the presence of type A reticulum cell sarcomas in the urinary bladder, uterus, ovaries, and vagina. The estimation of risk of 10e6 over background for malignant liver neoplasms using linear extrapolations showed a lower bound on the virtually safe dose (VSD) to be 2 ppb for the female mice and 1 ppb for the male mice. For benign and malignant liver tumors together, the lower bound on the VSD was essentially the same as for malignant liver neoplasm alone. Under the conditions of the experiment described above, gentian violet appears to be a carcinogen in mice at several different organ sites. 0 1985 hi* 0f Toxicology. ' Pathology Associates, Inc., National Center for Tox-Fuji& (1977) has shown gentian violet to icological Research, Jefferson, Ark. 72079. be mutagenic to Bacillus subfilis, Escherichia ' System Development Corp., National Center for Tox-coli, and Salmonella typhimurium. Au et al.

Mycobacterium smegmatis mc2 155 fbiC and MSMEG_2392 are involved in triphenylmethane dye decolorization and coenzyme F420 biosynthesis

“…It is soluble and stable in water at high concentrations. While it is toxic to mammalian cells (Bose et al, 2004(Bose et al, , 2005Fessard et al, 1999;Gupta et al, 2003;Littlefield et al, 1985;Stammati et al, 2005), several species of fungi and bacteria are known to decolorize and degrade malachite green through a variety of pathways.…”

IncP-1β plasmids of Comamonas sp. and Delftia sp. strains isolated from a wastewater treatment plant mediate resistance to and decolorization of the triphenylmethane dye crystal violet

“…CV is harmful in different ways to humans and animals (Docampo & Moreno, 1990). In solution it is a cation able to interact with nucleophilic compounds such as negatively charged DNA (Littlefield et al, 1985). Binding of CV to DNA can lead to chromosomal damage and reduced expression of genes (Au et al, 1978), as well as increased growth of tumour cells in mice (Littlefield et al, 1985) and some fish (Chen et al, 2007).…”

“…In solution it is a cation able to interact with nucleophilic compounds such as negatively charged DNA (Littlefield et al, 1985). Binding of CV to DNA can lead to chromosomal damage and reduced expression of genes (Au et al, 1978), as well as increased growth of tumour cells in mice (Littlefield et al, 1985) and some fish (Chen et al, 2007). Moreover, CV can even cause blindness and kidney damage in humans (Mittal et al, 2010).…”

Accurate Determination of Malachite Green and Leucomalachite Green in Fish using Isotope Dilution Liquid Chromatography/Mass Spectrometry (ID-LC/MS)

“…4,5 MG is related structurally to other carcinogenic triphenylmethane dyes: gentian violet, a thyroid and liver carcinogen in rodents, and pararoaniline, a bladder carcinogen in humans. 6,7 Hence, the use of MG has been prohibited in Europe, United States or Canada due to its suspected carcinogenic properties. The European a Current address: COSMAX, Hwaseong-si, Gyeonggi-do 902, Korea Commission requires that the minimum required performance limit for the analysis of MG in fish products was set at 2 μg/kg as the sum of MG and LMG.…”