Fizzy brown soda or tea in a clear glass with ice cubes and citrus wedge

4-Methylimidazole (4-MEI)

General

4-Methylimidazole (4-MEI) is a byproduct formed through the Maillard browning reaction which occurs during the cooking, roasting, or caramelization processes of some foods and beverages. For example, it can form during roasting of coffee beans and grilling of meats. It can also form during manufacturing, such as production of caramel coloring (i.e. Class III and IV caramel coloring).

It is commonly found in coffee, processed meats, baked goods, caramel-colored soft drinks (e.g., colas), some beers and teas. These foods and beverages either contain added caramel color or 4-MEI as a result of thermal process during production (Folmer et al., 2018).

Research in animal studies indicates that 4-MEI may pose carcinogenic risks, specifically lung and liver tumors (Akbari et al., 2023). The International Agency for Research on Cancer (IARC) has evaluated the carcinogenicity of 4-MI and considered 4-MI as "possibly carcinogenic to humans" (i.e. Group 2B) solely based on the studies in animals.

The European Food Safety Authority (EFSA) has also evaluated the safety of caramel colorings and concluded that they are neither genotoxic (i.e., capable of causing damage to DNA), nor carcinogenic and that there is no evidence to show that they have any adverse effects on human reproduction or for the developing child. 

The FDA requires that the labels of food containing non-certified color additives, such as caramel coloring, declare the color additives in the ingredients statement either by name or with a general term such as “artificial color” or “color added” unless otherwise indicated. Foods that have “caramel coloring” on a food label do not necessarily contain 4-MEI, because the term “caramel coloring” may be used to describe any class of caramel coloring. Class III and IV caramel coloring contain 4-MEI; Class I and Class II caramel coloring do not contain 4-MEI.

In 2011, 4-MEI was put on the California Proposition 65 list because the National Toxicology Program found long-term exposure to high concentrations of 4-MEI increased lung tumors in laboratory mice. Businesses must provide a warning if they manufacture or sell products in California that cause exposures to significant amounts of 4-MEI. A daily exposure threshold is set at 29 µg/day which is the safe harbor/no significant risk level (NSRL) developed by the Office of Environmental Health Hazard Assessment (OEHHA). Products that expose the public to levels of 4-MEI that are less than the safe harbor do not require warnings.

Laboratories typically use the following techniques to measure 4-MEI levels by Gas Chromatography-Mass Spectrometry (GC-MS), High-Performance Liquid Chromatography (HPLC) or Liquid Chromatography coupled with Tandem Mass Spectrometry (LC-MS/MS). These methods are precise, but the accuracy of measurements depends on proper calibration, sample preparation, and adherence to standardized protocols.

Guidance for Industry

Food processors can employ several strategies to reduce 4-MEI:

  1. Ingredient Selection: Avoiding or reducing the use of certain caramel colorings. Use natural coloring alternatives that do not produce 4-MEI.
  2. Temperature and Time Control: Optimizing thermal processing conditions to limit 4-MEI formation.
  3. Monitoring: Implementing stringent monitoring processes and regular testing of products for 4-MEI levels.

Information for Consumers to Reduce Exposure

Consumers can reduce their exposure to 4-MEI by checking product labels for caramel color (Class III or IV), opting for beverages and foods that use natural colorants, and limiting the intake of caramel-colored soft drinks and processed foods.

Resources