3-Monochloropropane-1,2-diol (MCPD) Esters and Glycidyl Esters
3-monochloropropane-1,2-diol esters (3-MCPDE) and glycidyl esters (GE) are contaminants that can occur in edible oils, such as vegetable oils, and foods made from these oils. Both food manufacturers and consumers use edible oils as an ingredient in foods and for cooking. During industrial refining, 3-MCPDE and GE can form in edible oils when the oils are heated at very high temperatures to remove unwanted tastes, colors, or odors. The highest concentrations typically occur in refined palm oil and palm olein oil, but 3-MCPDE and GE also are found in other refined vegetable oils (such as safflower, coconut, sunflower, and soybean oils) and refined marine oils (such as fish oils).
During digestion, 3-MCPDE and GE break down to the organic chemicals 3-monochloropropane-1,2-diol (3-MCPD) and glycidol. In studies of rodents, 3-MCPD caused adverse effects on kidneys and male reproductive organs, and both 3-MCPD and glycidol caused cancer. To better understand the potential risks of 3-MCPDE and GE in foods for humans, the FDA has developed methods to measure these contaminants in foods, conducted surveys of edible oils and other foods containing edible oils, and researched the potential adverse health effects of 3-MPCDE and GE.
Refined vegetable oils are a major component of infant formula, because fats from added oils are important for infant nutrition. Since infants are a vulnerable population, FDA work has focused on measuring levels of 3-MCPDE and GE in infant formulas to ensure the safety of infant formula. The FDA has also engaged with industry to share information on the health effects of 3-MCPDE and GE and the availability of mitigation methods for refined edible oils and infant formula to help reduce the levels of these contaminants.
In addition, the Codex Alimentarius Commission, in which FDA participates, developed recommendations for industry on reducing 3-MCPDE and GE in refined oils and foods. As chair of a Codex working group, the U.S. helped to develop a code of practice that outlines agricultural, refining, post-refining, and processing measures that industry can use to reduce levels of 3-MCPDE and GE in refined oils and foods made from refined oils.
In laboratory studies, 3-MCPDE and GE break down in the digestive tract to 3-MCPD and glycidol. Research studies in rodents show that 3-MCPD primarily affects the kidney and the testes and can cause cancer. There is clear evidence that glycidol is a carcinogen in rodents from research by the U.S. National Toxicology Program. The International Agency for Research on Cancer classifies 3-MCPD and glycidol as possible and probable human carcinogens, respectively.
In 2016, the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives (JECFA) conducted an evaluation of 3-MCPDE/3-MCPD and GE/glycidol and the evaluation included participation by FDA scientists. JECFA derived a provisional maximum tolerable daily intake (PMTDI) of 4 µg/kg bw/day for 3-MCPDE/3-MCPD. For GE, JECFA determined that the lower end margins of exposure (MOEs) for infants, children, and adults may be a health concern. Based on this assessment, JECFA recommended reducing 3-MCPDE and 3-MCPD in infant formula and GE and glycidol in fats and oils, particularly when used in infant formula.
As new research on 3-MCPDE and GE becomes available, FDA experts will consider the research in their continued evaluation of the effects of 3-MCPDE and GE on human health.
As part of the FDA research program on 3-MCPDE and GE, FDA scientists have developed and validated analytical methods to measure 3-MCPDE and GE and used the methods to conduct surveys of refined vegetable oils and infant formulas. FDA scientists also conducted an exposure assessment of 3-MCPDE and GE from consumption of infant formula. Research publications of the FDA’s methods and results are presented in the subsequent section.
The FDA has focused its testing efforts on infant formula because infants are a vulnerable population, infant formula contains relatively large amounts of oil (about 25-30%) to support infants’ nutritional needs, and for some infants, infant formula is a sole food source. Because of the combined efforts of industry and the FDA, average 3-MCPDE and GE levels in infant formula in the U.S. have declined over the last several years.
Between 2013-2016, FDA scientists surveyed 98 infant formula samples including both milk- and plant-based formulas. Using the data collected, the FDA conducted an exposure assessment estimating the average 3-MCPDE and GE exposures to infants (0-6 months), considering all types and brands of formula, as 7-10 µg/kg bw/day for 3-MCPDE and 2 µg/kg bw/day for GE, with the 3-MCPDE levels exceeding the 4 µg/kg bw/day recommended JECFA level. Following this finding, FDA scientists initiated conversations with the infant formula industry and brought concerns about the elevated levels in the 2013-2016 sample set to industry’s attention.
Between 2017-2019, to determine if infant formula manufacturers had reduced 3-MCPDE and GE levels in infant formulas, FDA scientists surveyed and analyzed an additional 222 samples of infant formula from the four largest U.S. infant formula manufacturers. Based on FDA’s testing of products on the market from 2017-2019, three U.S. manufacturers have successfully reduced 3-MCPDE and GE levels in their infant formula products to levels consistent with levels seen in infant formulas internationally. As a result of our continued dialogue with infant formula manufacturers, the FDA anticipates almost all U.S. formula products will have reduced levels by early 2021.
Infant Formula, 2016-2020: FDA researchers developed a method to analyze 3-MCPDE and GE in liquid and powdered infant formula.
Between 2013-2016, using this analytical method, the FDA surveyed 98 infant formula samples for 3-MCPDE and GE concentrations. Data from this survey were used to conduct a dietary exposure assessment for 3-MCPDE and GE in infant formulas in the United States. The results indicate that US infant exposures to 3-MCPDE and GE from consumption of formulas could potentially be reduced if manufacturers used oils produced with mitigation measures.
Between 2017-2019 another survey was conducted to evaluate concentrations of 3-MCPDE and GE in 222 infant formulas purchased in the United States. Compared to the survey results from 2013-2016, contaminant concentrations in infant formula have decreased in products produced by most US manufacturers.
Processing Contaminants in Edible Oils, 2013: FDA scientists developed a method for analyzing 3-MCPDE and GE. The method was used to determine concentrations of 3-MCPDE and GE in 116 retail and industrially produced edible oils purchased in the United States from 2011-2013. The highest concentrations for both 3-MCPDE and GE were seen in refined palm oil and palm olein samples.
The FDA led an international group of scientists and regulators to develop an international (Codex) Code of Practice (COP) for the Reduction of 3-MCPDE and GE in Refined Oils and Food Products Made with Refined Oils. The information used to develop the COP comes from U.S. industry, as well as international countries and organizations. Because many factors affect the likelihood of oils to form 3-MCPDE and GE during refining—including climate, soil and growth conditions of oil-producing plants, plant genotype, harvesting techniques, and processing conditions—the COP addresses agricultural, refining, post-refining, and processing measures that industry can implement to reduce 3-MCPDE and GE levels.
The FDA has engaged with U.S. industry to learn about mitigation efforts and to encourage reductions in 3-MCPDE and GE levels in U.S. infant formulas.
The FDA evaluates contaminants in food on a case-by-case basis, using the best available science including toxicity data, consumption information, and contaminant levels in the food. The FDA encourages manufacturers to take advantage of readily available mitigation approaches to lower contaminant levels.
International Scientific Activities