Reproductive and developmental toxicity risk assessment for 4-methylimidazole

4-Methylimidazole (4-MEI) is present in caramel color for food and beverages and as a by-product of the thermal treatment of food. A risk assessment for 4-methylimidazole reproductive and developmental effects was conducted using data from a National Toxicology Program Reproductive Assessment by Continuous Breeding and using 90th percentile dietary exposure data from the U.S. Food and Drug Administration. The National Toxicology Program reported reproductive and developmental toxicity in Sprague Dawley rats from high dietary exposure to 4-MEI. Using the benchmark dose method of modeling dose-response curves, the lowest margin of exposure (MOE) was 1489. Using the traditional no observed adverse effect level (NOAEL)/lowest observed adverse effect level (LOAEL), the margin of exposure at the 90th percentile human consumption was 735. MOEs of 100 or greater are considered to be of low concern. In conclusion, human exposure to 4-MEI in the diet in the United States is not expected to confer risk to reproduction or development.