Research Article: Caramel Color in Soft Drinks and Exposure to 4-Methylimidazole: A Quantitative Risk Assessment

Date Published: February 18, 2015

Publisher: Public Library of Science

Author(s): Tyler J. S. Smith, Julia A. Wolfson, Ding Jiao, Michael J. Crupain, Urvashi Rangan, Amir Sapkota, Sara N. Bleich, Keeve E. Nachman, Maciej Buchowski.


Caramel color is added to many widely-consumed beverages as a colorant. Consumers of these beverages can be exposed to 4-methylimidazole (4-MEI), a potential carcinogen formed during its manufacture. California’s Proposition 65 law requires that beverages containing 4-MEI concentrations corresponding to exposures that pose excess cancer risks > 1 case per 100,000 exposed persons (29 μg 4-MEI/day) carry warning labels. Using ultrahigh-performance liquid chromatography-tandem mass spectrometry, we assessed 4-MEI concentrations in 12 beverages purchased in California and a geographically distant metropolitan area (New York) in which warning labels are not required. In addition, we characterized beverage consumption by age and race/ethnicity (using weighted means calculated from logistic regressions) and assessed 4-MEI exposure and resulting cancer risks and US population cancer burdens attributable to beverage consumption. Data on beverage consumption were obtained from the National Health and Nutrition Examination Survey, dose-response data for 4-MEI were obtained from the California Environmental Protection Agency Office of Environmental Health Hazards Assessment, and data on population characteristics were obtained from the U.S. Census Bureau. Of the 12 beverages, Malta Goya had the highest 4-MEI concentration (915.8 to 963.3μg/L), lifetime average daily dose (LADD – 8.04×10-3 mg/kgBW-day), lifetime excess cancer risk (1.93×10-4) and burden (5,011 cancer cases in the U.S. population over 70 years); Coca-Cola had the lowest value of each (4-MEI: 9.5 to 11.7μg/L; LADD: 1.01×10-4 mg/kgBW-day; risk: 1.92×10-6; and burden: 76 cases). 4-MEI concentrations varied considerably by soda and state/area of purchase, but were generally consistent across lots of the same beverage purchased in the same state/area. Routine consumption of certain beverages can result in 4-MEI exposures > 29 μg/day. State regulatory standards appear to have been effective in reducing exposure to carcinogens in some beverages. Federal regulation of 4-MEI in caramel color may be appropriate.

Partial Text

Soft drinks, including sodas, are widely consumed in the United States [1,2]. A common ingredient in many soft drinks (e.g., colas, root beers, iced teas) is caramel color [3,4] produced with ammonium compounds (i.e., caramel color type IV)[5,6]. The use of these compounds to manufacture caramel color can result in the formation of 4-methylimidazole (4-MEI)[7]. In recent years, evidence for the carcinogenicity of 4-MEI has raised concerns about uses of caramel color type III and IV that may expose consumers to 4-MEI and increase cancer risk [8–11].

Our study did not involve human or animal subjects.

This is the first study to estimate 4-MEI concentrations in common soft drinks as well as corresponding cancer risks and burdens. Based on 4-MEI concentrations observed in beverage samples from this study, it appears that 4-MEI exposures associated with average rates of soft drink consumption pose excess cancer risks exceeding one case per 1,000,000 exposed individuals, which is a common acceptable risk goal used by some U.S. federal regulatory agencies [20–22]. Specifically, consumption of Malta Goya, Pepsi, Diet Pepsi and Pepsi One resulted in 4-MEI exposures with associated risks exceeding one excess case per 10,000 exposed individuals, suggesting that the risk can greatly exceed this threshold.