Preplanned Studies: Exposure to Chloropropanols and Their Fatty Acid Esters and Glycidyl Fatty Acid Esters in the Sixth Total Diet Study — China, 2016–2019

Chloropropanols and their derivatives, including fatty acid esters and glycidyl fatty acid esters (GEs), are prevalent contaminants arising from food processing. Notably, chloropropanols encompass both mono- and dichloro-substituted variants such as 2-monochloropropane-1,3-diol (2-MCPD) and 3-monochloropropane-1,2-diol (3-MCPD), as well as 1,3-dichloro-2-propanol (1,3-DCP) and 2,3-dichloro-1-propanol (2,3-DCP), each with corresponding fatty acid esters. These compounds are linked to reproductive toxicity, genotoxicity, and carcinogenicity. Evidence suggests that their fatty acid esters can be converted by lipases into free chloropropanols or glycidol, resulting in toxicity within the gastrointestinal tract (1). Given that dietary intake is the principal route by which these contaminants are ingested, they present a growing concern for food safety. Consequently, an assessment of dietary exposure to chloropropanols and their esters was performed as part of the Sixth China Total Diet Study (TDS) from 2016 to 2019, as detailed by Lyu et al (2). This assessment discovered that 3-MCPD esters and GEs are the most frequently detected contaminants in composite food samples. The escalating concern about the potential health hazards linked to GEs emphasizes the need for robust strategies to mitigate dietary exposure.

3-MCPD has been classified as a “possible human carcinogen” (Group 2B) by the International Agency for Research on Cancer (IARC) (3). Despite the recognized risk posed by 3-MCPD, there is limited data on the direct toxicity of other chloropropanols and their esters. Reflecting concerns over the long-term carcinogenic potential of 3-MCPD, the Joint FAO/WHO Expert Committee on Food Additives revised the provisional maximum tolerable daily intake (PMTDI) to 4 µg/kg body weight (BW) per day in 2017 (1). In 2018, the European Food Safety Authority (EFSA) established the tolerable daily intake for 3-MCPD and its esters (expressed as 3-MCPD equivalents) at 2 µg/kg BW per day, owing to the comparable toxicity of the chloropropanol esters and the free forms (4). This study conservatively applies the PMTDI of 4 µg/kg BW per day as a health-based guidance value (HBGV) for both 2-MCPD and its esters (expressed as 2-MCPD equivalents), assuming their toxicities are identical to those of 3-MCPD and its esters. Currently, food safety authorities have not set HBGVs for GEs. However, the EFSA advocates using a margin of exposure (MOE) approach for assessing the health risks from GE exposure, considering an MOE of 25,000 or higher as indicative of a low health concern (5).

The dietary exposure assessment to chloropropanols, their fatty acid esters, and GEs was performed focusing on a typical male adult from China (18–45 years old, 63 kg BW, engaged in light physical activity). This assessment spanned 24 provincial-level administrative divisions (PLADs) across 12 food categories within the scope of the Sixth China TDS. The study incorporated an analysis of seven chloropropanols and several esters, including 2-MCPD, 3-MCPD, 1,3-DCP, 2,3-DCP, 2-MCPD esters, 3-MCPD esters, and GEs. According to prior research, GEs were transformed into 3-bromopropanediol (3-MBPD) esters via bromination, and these, along with 2-MCPD esters and 3-MCPD esters, were hydrolyzed to their corresponding free forms for analysis. These forms were detected and quantified as glycidol equivalents, 2-MCPD, and 3-MCPD respectively (6). For detection purposes, derivatization was combined with quantification using internal standards through GC-MS/MS. The limit of detection (LOD) for chloropropanols, their esters, and GEs in dietary samples were established at 2.0, 4.0, and 4.0 µg/kg, respectively. When conducting descriptive statistical analyses of contamination levels and exposure, concentration values for specific food categories were set to 0.0 µg/kg if target contaminants were not detected across all samples within a category. Conversely, if levels were below the LOD, concentrations were calculated as half of the LOD value.

In this study, neither 1,3-DCP nor 2,3-DCP were detected in any of the 288 composite food samples analyzed. 2-MCPD was found only in five samples at concentrations near the LOD, leading to the exclusion of these chloropropanols from dietary intake assessment in this investigation. Table 1 presents summarized data on the contamination levels of detected chloropropanols, chloropropanol esters, and GEs across various food categories. The detection frequency (DF) of 3-MCPD esters (free 3-MCPD form) was notably higher at 87.2%, as was that of GEs (free glycidol form) at 74.3%, compared to 2-MCPD esters (free 2-MCPD form) at 41.3% and 3-MCPD at 30.6% in all samples evaluated. Among the 12 food categories, eggs exhibited the highest contamination levels for all target chloropropanol esters, with a geometric mean [95% confidence interval (95% CI)] of 79.7 (78.3, 81.1) µg/kg for 3-MCPD esters and 17.2 (15.5, 18.8) µg/kg for 2-MCPD esters. Vegetables followed, showing levels of 64.8 (63.9, 65.7) µg/kg for 3-MCPD esters and 15.7 (14.6, 16.7) µg/kg for 2-MCPD esters. The highest levels of GEs were found in meat with a geometric mean (95% CI) of 61.0 (60.3, 61.7) µg/kg, with vegetables next at 56.5 (55.5, 57.4) µg/kg (Figure 1). However, the peak concentrations for the esters were identified in an egg sample from Zhejiang Province — 4,390.0 µg/kg for 3-MCPD esters, 1,294.0 µg/kg for GEs, and 837.0 µg/kg for 2-MCPD esters. Compared to other food categories, vegetables displayed relatively higher geometric mean (95% CI) levels of 3-MCPD at 9.7 (8.4, 11.1) µg/kg, followed by potatoes at 3.5 (2.3, 4.7) µg/kg and meat at 2.3 (1.2, 3.3) µg/kg, with the highest concentration found in a vegetable sample from Guizhou Province (88.9 µg/kg).

Figure 1. 

Estimated dietary intakes and contributions of various composite food categories of 3-MCPD, 2-MCPD esters, and 3-MCPD esters for adult males in 24 PLADs from the Sixth China TDS, 2016–2019.

Note: Group A=3-MCPD, 2-MCPD and their esters; Group B=3-MCPD and its esters; Group C=2-MCPD and its esters.

Abbreviation: PLADs=provincial-level administrative divisions; 3-MCPD=3-monochloropropane-1,2-diol; 2-MCPD=2-monochloropropane-1,3-diol; TDS=Total Diet Study.

Dietary exposure estimates to chloropropanols and their esters during the Sixth China TDS were derived from food consumption and contamination level data. The estimated dietary intakes of chloropropanols, chloropropanol esters, and GEs across the 24 PLADs are detailed in Supplementary Tables S1 and S2. The average and high (95th percentile) dietary intakes were as follows: 3-MCPD esters (1.07, 2.20 µg/kg BW per day), GEs (0.79, 1.42 µg/kg BW per day), and 2-MCPD esters (0.26, 0.63 µg/kg BW per day) were all higher than those for 3-MCPD (0.14, 0.28 µg/kg BW per day). The highest dietary intake recorded for 3-MCPD esters was 3.51 µg/kg BW per day in Zhejiang Province, with Fujian Province following at 2.27 µg/kg BW per day. Despite eggs exhibiting the highest mean contamination level across the 24 PLADs, vegetables (43.5%) and cereals (15.1%) contributed more to the total intake of 3-MCPD esters than eggs (12.1%) due to their significantly larger consumption. The highest recorded intake of GEs was 2.04 µg/kg BW per day in Shaanxi Province, succeeded by Zhejiang Province (1.45 µg/kg BW per day). Similar to 3-MCPD esters exposure, GEs ingestion predominantly came from vegetables, though meat contributed more to GEs than it did to 3-MCPD or 2-MCPD esters. For 2-MCPD esters, the maximum intake was 0.90 µg/kg BW per day in Fujian Province, with the minimum at 0.06 µg/kg BW per day in Liaoning Province. Although the average intake of 3-MCPD was lower than 2-MCPD esters, the range of 3-MCPD intake (0.05 to 0.64 µg/kg BW per day) paralleled that of 2-MCPD esters. Notably, high intakes of 3-MCPD were observed in Guizhou Province and Hunan Province, at 0.64 and 0.28 µg/kg BW per day, respectively.