Chronic toxicity and carcinogenicity studies of gentian violet in mice

Abstract

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 B6C3F1 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 after 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 mortality due to liver neoplasms, prevalence of liver neoplasms, and 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 10(-6) 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.

Effects of Acridine Derivatives on Ca2+ Uptake by Candida albicans

“…However, triphenylmethane derivatives have been banned in almost all the world, mainly because of studies that revealed chronic toxicity and carcinogenicity of gentian violet in mice [9].…”

Biotransformation of Malachite Green by the FungusCunninghamella elegans

“…Malachite green is highly toxic to mammalian cells; it promotes hepatic tumor formation in rodents and also causes reproductive abnormalities in rabbits and fish (13,24). The structural similarity of malachite green to other carcinogenic triphenylmethane dyes also raises suspicion of carcinogenicity; gentian violet (crystal violet) is a thyroid and liver carcinogen in rodents (17), and pararosaniline is a bladder carcinogen in humans (7). Based on the potential for adverse human health effects, the U.S. Food and Drug Administration nominated malachite green as a priority chemical for carcinogenicity testing by the National Toxicology Program in 1993 (10).…”

Toxicokinetic and Mechanistic Considerations in the Interpretation of the Rodent Bioassay

“…Hyperplastic changes in this tissue (including adenomas) have been reported in mice for structurally and functionally diverse chemicals [gentian violet (70), aniline dyes (120), misoprostol (go), nalidixic acid (6 l), and spontaneous incidence (103)l. The literature is sparse in the area of possible mechanisms ofhyperplastic lesions in this tissue. It is plausible that the hormone sensitivity of this gland may be related to a cell proliferation response.…”