Toxicity and carcinogenicity studies of 4-methylimidazole in F344/N rats and B6C3F1 mice

Chan, Po-Chuen; Hill, Georgette D.; Kissling, Grace E.; Nyska, Abraham

doi:10.1007/s00204-007-0227-0

Cited by 15 publications

(23 citation statements)

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“…The toxicity of 4(5)-MI has been reported by the Natl. Toxicology Program (NTP 2007), due to research showing increased risk of lung tumors in a mouse study, as well as increased risk of tremors, ataxia, and anemia in rats (Chan and others 2006;Chan 2008). Thus, many researchers from regulatory agencies have focused on the carcinogenicity of 4(5)-MI.…”

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confidence: 99%

Effect of Various Food Additives on the Levels of 4(5)‐Methylimidazole in a Soy Sauce Model System

Lee

Hwang

et al. 2015

Journal of Food Science

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In this study, the effect of food additives such as iron sulfate, magnesium sulfate, zinc sulfate, citric acid, gallic acid, and ascorbic acid on the reduction of 4(5)-methylimidazole (4(5)-MI) was investigated using a soy sauce model system. The concentration of 4(5)-MI in the soy sauce model system with 5% (v/v) caramel colorant III was 1404.13 μg/L. The reduction rate of 4(5)-MI level with the addition of 0.1M additives followed in order: iron sulfate (81%) > zinc sulfate (61%) > citric acid (40%) > gallic acid (38%) > ascorbic acid (24%) > magnesium sulfate (13%). Correlations between 4(5)-MI levels and the physicochemical properties of soy sauce, including the amount of caramel colorant, pH value, and color differences, were determined. The highest correlations were found between 4(5)-MI levels and the amount of caramel colorant and pH values (r(2) = 0.9712, r(2) = 0.9378). The concentration of caramel colorants in 8 commercial soy sauces were estimated, and ranged from 0.01 to 1.34% (v/v).

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confidence: 99%

Effect of Various Food Additives on the Levels of 4(5)‐Methylimidazole in a Soy Sauce Model System

Lee

Hwang

et al. 2015

Journal of Food Science

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“…The higher ROS production, especially hydrogen peroxide and superoxide, may be due to the mediation of cytochrome P450, which is recognized for promoting this increase 24 , since 4-MEI has a structure very similar to 2 and 3-methylfuran which has the cytochrome P 450 protein after its metabolism 25 . Similarly, high doses of paracetamol following cytochrome P450 metabolism generates a toxic metabolite known as N-acetyl-p-benzoquinoneimine, that can be conjugated with reduced glutathione and depleting its hepatic stores 26 .…”

Section: Discussionmentioning

confidence: 99%

“…This oxidative stress damage could be observed by histological analysis in both liver and kidney of mice caused by C-IV 3g/kg administration, where diffuse mild paracentral hydropic degeneration could be identified at liver and a possible glomerulonephritis, moderate multifocal proliferative membrane, low glomerulus count at kidney tissue. In addition, studies show that animals treated with 2-methylimidazole develop renal lesions consisting of hemosiderin, which is most evident in male mice 25 . These alterations are linked to increased hepatic lipid peroxidation and renal ROS damages.…”

Section: Discussionmentioning

confidence: 99%

Caramel Dye IV Induces Oxidative Stress Damage In Liver And Kidney From Mice

Marins

Silva

Rosa

et al. 2019

Preprint

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24Caramel dye IV (C-IV) is a synthetic organic product, does not present nutritional, ergogenic, or 25 technological factors, but leads to reactive oxygen species (ROS), causing damage to a wide range 26 of molecules, leading to cancer, cardiovascular and neurodegenerative diseases development. We 27 aimed to verify the effects of different doses of C-IV dye on the markers of oxidative stress in the 28 liver and kidneys from male Swiss CF-1 mice, divided into 4 experimental groups: control; C-IV 29 0.3g/kg; C-IV 1g/kg and C-IV 3g/kg. We found that 3 g/Kg of C-IV dye promote oxidative damage 30 in liver and kidney homogenates, evidenced by the increase of lipid peroxidation, reduction of free 31 SH groups, and higher ROS production. As a consequence, increased superoxide dismutase and 32 acetylcholinesterase enzymes activities were detected. These damages were confirmed through 33 histology images. These results indicate that daily doses might induce oxidative stress damages and 34 possible lead to chronic diseases development. 35 36

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“…In rats, around 1250-5000 ppm (estimated daily consumption: 60-250 mg/Kg of body weight) of 4-MI were dosed, and the exposed rats exhibited the abnormalities, including seizures, hyperactivity and loss of body weight. 29 In mice, the exposure dosages were 312-1250 ppm (~40-170 mg/Kg of body weight). 29 Young calves exposed to a higher dose (400 mg/Kg body weight) of 4-MI displayed some acute symptoms, including tremors, hyperexcitability, and muscle fasciculations.…”

Section: -Mi Disturbs Muscle-specific Gene Expressionmentioning

confidence: 99%

“…29 In mice, the exposure dosages were 312-1250 ppm (~40-170 mg/Kg of body weight). 29 Young calves exposed to a higher dose (400 mg/Kg body weight) of 4-MI displayed some acute symptoms, including tremors, hyperexcitability, and muscle fasciculations. 9 The half lethal doses of 4-MI for mouse, rabbit and chicken were estimated as 120~751 mg/Kg.…”

Section: -Mi Disturbs Muscle-specific Gene Expressionmentioning

confidence: 99%

Embryonic exposure to 4‐methylimidazole leads to zebrafish myofibril misalignment

Tsai

Sun

Ding

et al. 2018

Environmental Toxicology

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4‐methylimidazole (4‐MI) is an imidazole‐derived organic chemical compound that can be used as a raw material in the manufacture of diverse chemicals and has been identified as an ingredient of caramel color in soybean sauce, beers, and other soft drinks. The aim of the present study was to investigate the teratogenic effects of 4‐MI during zebrafish embryogenesis. Zebrafish embryos were treated with different dosages of 4‐MI (0‐120 mM) for different exposure durations (12‐60 hours). The percentages of embryos with malformed phenotypes increased as the exposure dosages and duration time of 4‐MI increased. We also used immunofluorescence and transmission microscopy to evaluate the subtle changes in the myofibril alignment and ultrastructure of muscle organization. Our data showed that 4‐MI treatment disturbs muscle fiber alignment. Electron microscopy data indicated that Z‐lines were undetectable in the 4‐MI‐treated embryos. Although the thick and thin filaments were visible, they were all disorganized. In addition, zebrafish embryos treated by 4‐MI exhibited aberrant expression of 2 muscle‐specific genes, myod and myogenin. Taken together, we concluded that early exposure to 4‐MI affects zebrafish myogenesis, especially in myofibril alignment.

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Toxicity and carcinogenicity studies of 4-methylimidazole in F344/N rats and B6C3F1 mice

Cited by 15 publications

References 0 publications

Effect of Various Food Additives on the Levels of 4(5)‐Methylimidazole in a Soy Sauce Model System

Effect of Various Food Additives on the Levels of 4(5)‐Methylimidazole in a Soy Sauce Model System

Caramel Dye IV Induces Oxidative Stress Damage In Liver And Kidney From Mice

Embryonic exposure to 4‐methylimidazole leads to zebrafish myofibril misalignment

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