What are the health risks associated with food contamination with 3-MCPD, 2-MCPD and glycidyl fatty acid esters?

3-monochloropropanediol (3-MCPD) and 2-monochloropropanediol (2-MCPD) are chemically classified as chloropropanols. A characteristic feature of this group of substances is that they have a glycerol backbone in which a hydroxyl group is replaced by a chlorine atom. In 3-MCPD, the chlorine atom is located at position 3, and in 2-MCPD at position 2. The fatty acid esters consist of chloropropanol esterified with one or two fatty acid residues (mono- and diesters).

The chemical structure of glycidol has the same glycerol backbone as chloropropanols, but has an epoxide structure instead of the chlorine atom. Glycidyl fatty acid esters are correspondingly compounds of glycidol esterified with a fatty acid (monoester). 

The substances have been detected in numerous heated food items, for example in darkly toasted bread, in the crust of bread, or in soy sauces. Free 3-monochloropropanediol (3-MCPD) or free 2-monochloropropanediol (2-MCPD) can be formed when food containing both fat and salt is exposed to high temperatures during the manufacturing process. According to current knowledge, the fatty acid esters of 2-MCPD, 3- MCPD and glycidol are mainly produced during the heat treatment of vegetable fats and oils for the purpose of purification and refinement. Raw oils still contain various accompanying substances which are undesirable for reasons including smell and taste, and these are therefore removed. Refined edible oils and fats such as palm oil or palm fat may therefore contain 2-MCPD, 3-MCPD and glycidyl fatty acid esters. 

In 28-day toxicity studies in rats, repeated oral administration of high doses of 2-MCPD caused damage to smooth muscle tissue, particularly in the heart muscle (cardiotoxicity). Harmful effects were also observed in the kidneys of the laboratory animals (nephrotoxicity). However, the toxicological data currently available for 2-MCPD and its fatty acid esters is incomplete. Long-term studies on dose-dependent toxicity are particularly needed in order to derive a health-based guidance value (HBGVshort forHealth-Based Guidance Value) as part of a risk assessment. In addition, further information on the modeClose dialogmodeModeTo glossary of action and toxicokinetics is lacking.

The situation is different for 3-MCPD and its fatty acid esters. A study on oral bioavailability in rats has shown that 3-MCPD fatty acid esters are almost completely cleaved during absorption in the intestine, releasing 3-MCPD. In long-term toxicological studies, an increase in cell number (hyperplasia) in the renal tubules was observed as the most sensitive endpoint after administration of 3-MCPD to laboratory animals. At higher doses, an increase in benign tumours was observed in the treated animals. No genotoxic effects have been demonstrated for free 3-MCPD. Based on current knowledge, it can therefore be assumed that the carcinogenic effects observed in the animal study with free 3-MCPD only occur at higher doses.

In 2018, EFSAshort forEuropean Food Safety Authority conducted an analysis of the dose-response relationships for 3-MCPD and its fatty acid esters. The increased occurrence of hyperplasia in the kidneys of male test animals was identified as the most sensitive endpoint.

Based on the available toxicological data, EFSAshort forEuropean Food Safety Authority determined a reference point (BMDLshort forBenchmark Dose Lower Confidence Limit₁₀) of 200 µgshort formicrogram/kgshort forkilogram body weight per day (male rats). BMDLshort forBenchmark Dose Lower Confidence Limit₁₀ is a toxicological estimate referring to the lowest dose in an animal experiment at which a specific effect increases by less than 10% with 95% certainty. Based on this value, EFSAshort forEuropean Food Safety Authority derived a tolerable daily intake (TDIshort forTolerable Daily Intake; Tolerable Daily Intake) for 3-MCPD of 2 µgshort formicrogram/kgshort forkilogram body weight. For consumers, this means that health impairments are not expected at a daily intake of up to 2 µgshort formicrogram 3-MCPD per kgshort forkilogram body weight. This includes the amount of 3-MCPD that is initially ingested as a fatty acid ester and then released in the intestine.

Glycidol has genotoxic and carcinogenic properties and has been classified as probably carcinogenic to humans by various scientific committees (IARC, MAK Commission). Studies on oral bioavailability have shown that glycidyl fatty acid esters are cleaved in the body, with glycidol being released almost completely. Therefore, from a toxicological point of view, glycidyl fatty acid esters are treated in the same way as glycidol. Due to the genotoxic potential of glycidol, no safe intake levels can be established for glycidyl fatty acid esters.

For substances that are genotoxic and carcinogenic, such as glycidol or glycidyl fatty acid esters, the general recommendation in the European Union (EU) is to minimise their concentrations in food as far as reasonably achievable (ALARA principle: as low as reasonably achievable).

The compounds were detected in refined edible oils and fats such as palm oil and palm fat, as well as in food made from them, such as margarine, baked goods and confectionery, and fried products, but also in various snack products, sweet spreads (nut nougat cream) and infant formula and follow-on formula.

A compilation of occurrence data in food on the German market from 2012-2017 can be found in the report of the BfRshort forGerman Federal Institute for Risk Assessment from 2020, which was updated again in 2022. High average concentrations of 3-MCPD were detected in fried fish sticks, fried herring, sweet spreads and pastries and croissants filled with these spreads. Sweet spreads and filled pastries also contained high concentrations of glycidyl fatty acid esters. 

Current data from the first German Total Diet (the BfRshort forGerman Federal Institute for Risk Assessment MEAL) study from 2019-2021 confirm that filled fine bakery wares still contain high concentrations of glycidyl fatty acid esters and 2- and 3-MCPD fatty acid esters. Fish fingers and French fries may also contain higher concentrations of these heat-induced contaminants, depending on the degree of browning and the type of heating (in a deep fryer, hot air fryer or oven).

In its opinions from 2016 and 2018, EFSAshort forEuropean Food Safety Authority concluded that exposureClose dialogexposureExposureTo glossary in the adult population does not exceed the newly established TDIshort forTolerable Daily Intake value of 2 µgshort formicrogram/kgshort forkilogram body weight per day. Only in younger age groups, in particular heavy consumers and infants who are exclusively fed infant formula, the intake of 3-MCPD and its fatty acid esters slightly exceeded the TDIshort forTolerable Daily Intake value. 

A 2020 assessment by the BfRshort forGerman Federal Institute for Risk Assessment, which was updated again in 2022, produced similar results based on more recent occurrence data and using nationally collected consumption data. For adults consuming normal or high amounts, the exposure assessment did not indicate any exceedance of the TDIshort forTolerable Daily Intake value of 2 μg/kgshort forkilogram body weight per day. In contrast, a significant exceedance of the TDIshort forTolerable Daily Intake was found for children and infants in some cases. Therefore, long-term consumption may pose an increased health risk to these population groups. External Link:https://www.bfr.bund.de/stellungnahme/gesundheitliche-risiken-durch-hohe-concentration-an-3-mcpd-und-glycidyl-fettsaeureestern-in-bestimmten-food-moeglich/

In order to reduce exposure to 3-MCPD and 3-MCPD fatty acid esters, Regulation (EU) No 2020/1322 has set maximum levels for certain food in the European Union (EU). These maximum levels have been in force since January 2021. Current data on the prevalence of 3-MCPD and 3-MCPD fatty acid esters in food from 2020–2022 from monitoring programmes in Member States indicate that, with good practice, lower levels of 3-MCPD and 3-MCPD fatty acid esters were already achieved in certain foods. Therefore, Regulation (EU) 2024/1003 has further lowered the maximum levels for 3-monochloropropanediol (3-MCPD) and 3-MCPD fatty acid esters in infant formula, follow-on formulae, foods for special medical purposes for infants and young children, and baby foods. These new maximum levels have been in force since 1 January 2025. 

At present, it is not yet possible to reliably assess the extent to which the risk to certain population groups has been reduced by the introduction or lowering of maximum levels. 

It is not possible to derive a safe intake level for glycidol and glycidyl fatty acid esters, as current knowledge does not allow to determine a threshold for carcinogenic substances with a DNA-reactive mode of action. Instead, risk characterisation is usually based on the margin of exposure (MOEshort forMargin of Exposure) concept. The MOEshort forMargin of Exposure is the quotient of a suitable toxicological reference point and the human exposure to the substance.

Based on studies in rats, a T25 value (the chronic dose at which 25% of the laboratory animals develop cancer in a specific tissue within their lifetime) of 10.2 mgshort formilligram per kgshort forkilogram bw and day was determined as the reference point for the carcinogenic effects of glycidol. Exposure to glycidol or glycidyl fatty acid esters is considered to pose little concern for public health if the margin of exposure (MOEshort forMargin of Exposure) determined on the basis of this reference point is 25,000 or more.

Based on this MOEshort forMargin of Exposure approach, EFSAshort forEuropean Food Safety Authority and the BfRshort forGerman Federal Institute for Risk Assessment concluded that younger population groups in particular, especially non-breastfed infants who are exclusively nourished with industrially produced formula (infant formula and follow-on formula), may ingest amounts of glycidol that are of concern for health. 

In order to reduce exposure to glycidyl fatty acid esters, Regulation (EU) No 2020/1322 established maximum levels for certain food in the European Union (EU). These maximum levels have been in force since January 2021. 

At present, it is not yet possible to reliably assess the extent to which the introduction of maximum levels has reduced the risk for certain population groups.

3-MCDP, 2-MCPD and their fatty acid esters, as well as glycidyl fatty acid esters, inevitably form when food containing both fat and salt is exposed to high temperatures. Accordingly, these substances are detected in numerous heated foods. In processed food that is already heated before it reaches the market, its concentrations can only be reduced by adjusting production and processing methods. To reduce intake from such food, consumers should eat certain foods known to have particularly high concentrations only in moderate amounts.

However, 3-MCDP, 2-MCPD and their fatty acid esters, as well as glycidyl fatty acid esters, can also form as process-related contaminants during domestic preparation of food . Meat or vegetables should therefore be fried in oil or fat without salt. Salt can then be added after frying. In the case of French fries and fish sticks, the degree of browning is also important (the browner they are, the higher the levels of these substances), but so is the type of heating (deep fryer, hot air fryer or oven). In the BfRshort forGerman Federal Institute for Risk Assessment-MEAL study, food that was pre-fried and/or fried in vegetable oils, such as fish fingers and French fries, had higher levels. 

Infant formula is formulated to meet the specific needs of children in the first months of life. It is manufactured from individual components in accordance with current scientific knowledge on nutritional requirements. Refined vegetable fats have long been used for the fat content. Due to the presence of 3-monochloropropanediol (3-MCPD), 2-monochloropropanediol (2-MCPD) and glycidyl fatty acid esters in these fats, these compounds are also found in infant formula. However, the concentrations must not exceed the maximum levels set at EU level.

In principle, there is no alternative to industrially manufactured infant formula for the nutrition of non-breastfed infants. This is the only way to ensure optimal nutrition when breastfeeding is not possible. The BfRshort forGerman Federal Institute for Risk Assessment therefore recommends that parents who do not breastfeed their infants continue to provide them with nutrition with specially formulated infant formula products as before, because these products contain the nutrients that are essential for infants in the correct proportions.