Does 4-methylimidazole have tumor preventive activity in the rat?

Murray and Associates, San Jose, CA 95138, USA.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association (Impact Factor: 2.9). 11/2010; 49(1):320-2. DOI: 10.1016/j.fct.2010.11.010
Source: PubMed


4-Methylimidazole (4-MEI) is found in a wide array of food products. The National Toxicology Program (NTP) recently conducted a two-year feeding cancer bioassay of 4-MEI in B6C3F(1) mice and F344/N rats. In rats, NTP found "equivocal evidence of carcinogenic activity" in females based on increased incidences of mononuclear cell leukemia and "no evidence of carcinogenic activity" in males. However, dose-related, statistically significant decreases in multiple tumors were observed in both male and female rats exposed to 4-MEI in the NTP bioassay. For example, 4-MEI was associated with a 25-fold decrease in the incidence of mammary tumors among high dose females. NTP noted briefly that the decreases in certain tumors, including mammary tumors, were greater than could be attributed to body weight alone. The present paper provides a more detailed evaluation of the evidence that 4-MEI exhibits tumor preventive activity in the rat based upon the results of the NTP bioassay. Reduced body weight offers a partial explanation for the reduction in tumors, but does not appear to be the primary cause of the decreased tumor incidences, indicating that 4-MEI itself may possess an ability to prevent tumor formation.

3 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: 2- and 4-methylimidazoles are present as contaminants in caramel colorings manufactured with ammonia catalysts. Both contaminants have been shown to induce cancer in animals and may be present in caramel colorings in amounts that exceed federal guidelines. California requires warning notices on products that could lead to consumption of more than 30 micrograms per day. The US Food and Drug Administration should bar the use of excessively contaminated caramel coloring in food.
    No preview · Article · Jul 2012 · International journal of occupational and environmental health
  • [Show abstract] [Hide abstract]
    ABSTRACT: Since the National Toxicology Program (NTP) identified 4(5)-methylimidazole [4(5)-MI] as a cancer causing chemical in 2007 and the State of California added it to the Proposition 65 list of compounds as a probable carcinogen in January 7, 2011, many researchers and regulatory agents have become focused on the presence of 4(5)-MI in foods and beverages. 4(5)-MI has been known to form in the Maillard reaction system consisting of a sugar and ammonia-a typical caramel-color preparation method for beverages. 4(5)-MI is identified in various beverages and sauces, which are colored with caramel, as well as in caramel color itself. Analysis of 4(5)-MI is extremely difficult due to its high water solubility but the analytical method for 4(5)-MI has progressed from conventional paper chromatography, gas chromatography, and gas chromatography/mass spectrometry to the most advanced high performance liquid chromatography/mass spectrometry. Various reports indicate that caramel colors and carbonated beverages contain 4(5)-MI in levels ranging from 0 to around 1,000 ppm and from 0 to about 500 ppm, respectively. Reports on the toxicity of 4(5)-MI at relatively high levels suggest that it may cause some adverse effects on human consumers.
    No preview · Article · Jan 2013 · Journal of Agricultural and Food Chemistry
  • [Show abstract] [Hide abstract]
    ABSTRACT: The potential carcinogenicity of 4-methylimidazole (4-MEI) was evaluated in a National Toxicology Program (NTP) rodent cancer bioassay in Fischer 344 rats and B6C3F1 mice (NTP, 2007; Chan et. al, 2008). The NTP concluded that there was "clear evidence of carcinogenic activity" in male and female mice, based on an increased incidence of lung tumors. The "category of evidence" that the NTP assigns to a rodent cancer bioassay outcome can have significant regulatory implications. This is especially important for 4-MEI, which forms in caramel colorings and other foods during cooking, with potential widespread human exposure in a broad spectrum of food and beverage products. A detailed analysis of all NTP mouse-lung-tumor-only carcinogens reveals that the proper call for lung tumors in the 4-MEI study should have been "some evidence" rather than "clear evidence" of carcinogenic activity for both male and female mice in order to be consistent with the NTP's interpretation of other mouse lung carcinogens showing a similar strength of response. Suggestions are given as to measures the NTP should consider in the preparation of some or all future Technical Reports in order to enhance consistency of interpretation of experimental results.
    No preview · Article · Mar 2013 · Regulatory Toxicology and Pharmacology
Show more