Abstract
Fatty acid esters of glycidol (glycidyl esters, GE) are processing contaminants in vegetable oils and fats. GE release the carcinogenic glycidol in the gastrointestinal tract. The assessment of health risks associated with dietary GE uptake is hindered by the inaccuracy of exposure estimations based on consumption and food content data. Alternatively, the internal exposure can be approximated by monitoring of human biomarkers of glycidol, for example, the hemoglobin adduct N-(2,3-dihydroxypropyl)-valine (DHP-Val). The quantification of DHP-Val levels in blood samples showed that human adults are exposed principally by foodstuffs and tobacco smoke. Reverse dosimetry allowed calculating the mean oral exposure for 11 German adults (0.94 μg/kg body weight) and 50 Swedish adolescents (1.4 μg/kg body weight). These values exceeded the median chronic exposure estimated from dietary surveys for the adult population (0.2 μg/kg body weight) and for adolescents (0.3 μg/kg body weight), which may be due to hitherto unknown sources of glycidol/GE. Data on DHP-Val in strict raw food eaters, who do not consume food heated to more than 42 °C, suggests that DHP-Val is also formed independently from the oral exposure to GE.
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Abbreviations
- DHP-Val:
-
N-(2,3-dihydroxypropyl)-valine
- DHP-Val-FTH:
-
N-(2,3-dihydroxypropyl)-valine fluorescein thiohydantoin
- EFSA:
-
European Food Safety Authority
- FITC:
-
Fluorescein-5-isothiocyanate
- FTH:
-
Fluorescein thiohydantoin
- GC-MS:
-
Gas chromatography-mass spectrometry
- GE:
-
Glycidyl esters
- Hb:
-
Hemoglobin
- LOD:
-
Limit of detection
- LOQ:
-
Limit of quantification
- SPE:
-
Solid-phase extraction
- UHPLC-MS/MS:
-
Ultra-high performance liquid chromatography-tandem mass spectrometry
References
Aasa J, Abramsson-Zetterberg L, Carlsson H, et al. The genotoxic potency of glycidol established from micronucleus frequency and hemoglobin adduct levels in mice. Food Chem Toxicol. 2017;100:168–74. https://doi.org/10.1016/j.fct.2016.12.022.
Aasa J, Vryonidis E, Abramsson-Zetterberg L, et al. Internal doses of glycidol in children and estimation of associated cancer risk. Toxics. 2019;7:7. https://doi.org/10.3390/toxics7010007.
Abraham K, Appel KE, Berger-Preiss E, et al. Relative oral bioavailability of 3-MCPD from 3-MCPD fatty acid esters in rats. Arch Toxicol. 2013;87:649–59. https://doi.org/10.1007/s00204-012-0970-8.
Abraham K, Hielscher J, Kaufholz T, et al. The hemoglobin adduct N-(2,3-dihydroxypropyl)-valine as biomarker of dietary exposure to glycidyl esters: a controlled exposure study in humans. Arch Toxicol. 2019;93:331–40. https://doi.org/10.1007/s00204-018-2373-y.
Abraham K, Hielscher J, Kuhlmann J, et al. Urinary excretion of 2/3-Monochloropropanediol (2/3-MCPD) and 2,3-Dihydroxypropylmercapturic acid (DHPMA) after a single high dose of fatty acid esters of 2/3-MCPD and glycidol: a controlled exposure study in humans. Mol Nutr Food Res. 2021;65:e2000735. https://doi.org/10.1002/mnfr.202000735.
Abraham K, Trefflich I, Gauch F, et al. Nutritional intake and biomarker status in strict raw food eaters. Nutrients. 2022;14:1725.
Appel KE, Abraham K, Berger-Preiss E, et al. Relative oral bioavailability of glycidol from glycidyl fatty acid esters in rats. Arch Toxicol. 2013;87:1649–59. https://doi.org/10.1007/s00204-013-1061-1.
Bakhiya N, Abraham K, Gurtler R, et al. Toxicological assessment of 3-chloropropane-1,2-diol and glycidol fatty acid esters in food. Mol Nutr Food Res. 2011;55:509–21. https://doi.org/10.1002/mnfr.201000550.
Barocelli E, Corradi A, Mutti A, et al. Comparison between 3-MCPD and its palmitic esters in a 90-day toxicological study. EFSA J. 2011;1–131. https://www.efsa.europa.eu/en/supporting/pub/en-187
Bentley SA, Lewis SM, White JM. Red cell survival studies in patients with unstable haemoglobin disorders. Br J Haematol. 1974;26:85–92.
Clewell HJ, Tan YM, Campbell JL, et al. Quantitative interpretation of human biomonitoring data. Toxicol Appl Pharmacol. 2008;231:122–33. https://doi.org/10.1016/j.taap.2008.04.021.
Ehrenberg L, Hiesche KD, Osterman-Golkar S, et al. Evaluation of genetic risks of alkylating agents: tissue doses in the mouse from air contaminated with ethylene oxide. Mutat Res. 1974;24:83–103.
European Food Safety Authority. Opinion of the Scientific Committee on a request from EFSA related to a harmonised approach for risk assessment of substances which are both genotoxic and carcinogenic. EFSA J. 2005;282:1–31.
European Food Safety Authority. Risks for human health related to the presence of 3-and 2-monochloropropanediol (MCPD), and their fatty acid esters, and glycidyl fatty acid esters in food. EFSA J. 2016;14:4426–584. https://doi.org/10.2903/j.efsa.2016.4426.
Fennell TR, Sumner SC, Walker VE. A model for the formation and removal of hemoglobin adducts. Cancer Epidemiol Biomark Prev. 1992;1:213–9.
Fennell TR, Sumner SC, Snyder RW, et al. Metabolism and hemoglobin adduct formation of acrylamide in humans. Toxicol Sci. 2005;85:447–59. https://doi.org/10.1093/toxsci/kfi069.
Hielscher J, Monien BH, Abraham K, et al. An isotope-dilution UPLC-MS/MS technique for the human biomonitoring of the internal exposure to glycidol via a valine adduct at the N-terminus of hemoglobin. J Chromatogr B. 2017;1059:7–13. https://doi.org/10.1016/j.jchromb.2017.05.022.
Honda H, Fujii K, Yamaguchi T, et al. Glycidol exposure evaluation of humans who have ingested diacylglycerol oil containing glycidol fatty acid esters using hemoglobin adducts. Food Chem Toxicol. 2012;50:4163–8. https://doi.org/10.1016/j.fct.2012.07.058.
Honda H, Törnqvist M, Nishiyama N, et al. Characterization of glycidol-hemoglobin adducts as biomarkers of exposure and in vivo dose. Toxicol Appl Pharmacol. 2014;275:213–20. https://doi.org/10.1016/j.taap.2014.01.010.
Inagaki R, Hirai C, Shimamura Y, et al. Formation of glycidol fatty acid esters in meat samples cooked by various methods. J Food Process Technol. 2016;7:557–62. https://doi.org/10.4172/2157-7110.1000557.
International Agency for Research on Cancer. Glycidol in some industrial chemicals. In: IARC monographs on the evaluation of carcinogenic risks to humans, vol. 77. Lyon: International Agency for Research on Cancer; 2000. p. 469–86.
Ishidao T, Kunugita N, Fueta Y, et al. Effects of inhaled 1-bromopropane vapor on rat metabolism. Toxicol Lett. 2002;134:237–43. https://doi.org/10.1016/s0378-4274(02)00171-6.
Janssen BG, Madhloum N, Gyselaers W, et al. Cohort profile: the ENVIRonmental influence ON early AGEing (ENVIRONAGE): a birth cohort study. Int J Epidemiol. 2017;46:1386–7. https://doi.org/10.1093/ije/dyw269.
Landin HH, Osterman-Golkar S, Zorcec V, et al. Biomonitoring of epichlorohydrin by hemoglobin adducts. Anal Biochem. 1996;240:1–6. https://doi.org/10.1006/abio.1996.0322.
Landin HH, Grummt T, Laurent C, et al. Monitoring of occupational exposure to epichlorohydrin by genetic effects and hemoglobin adducts. Mutat Res. 1997;381:217–26.
Landin HH, Tareke E, Rydberg P, et al. Heating of food and haemoglobin adducts from carcinogens: possible precursor role of glycidol. Food Chem Toxicol. 2000;38:963–9.
MAK Commission. List of MAK and BAT values 2021, vol. 57. MAK Collection. Publisso. 2021. https://doi.org/10.34865/mbwl_2021_eng.
Mathias PI, B’Hymer C. Mercapturic acids: recent advances in their determination by liquid chromatography/mass spectrometry and their use in toxicant metabolism studies and in occupational and environmental exposure studies. Biomarkers. 2016;21:293–315. https://doi.org/10.3109/1354750X.2016.1141988.
Monien BH, Abraham K. Levels of 2,3-dihydroxypropyl mercapturic acid (DHPMA) in human urine do not reflect the exposure to 3-chloro-1,2-propanediol (3-MCPD) or glycidol. Environ Res. 2022;211:112977. https://doi.org/10.1016/j.envres.2022.112977.
Monien BH, Abraham K, Nawrot TS, et al. Levels of the hemoglobin adduct N-(2,3-Dihydroxypropyl)-valine in cord and maternal blood: prenatal transfer of glycidol in the ENVIRONAGE birth cohort. Toxicol Lett. 2020;332:82–7. https://doi.org/10.1016/j.toxlet.2020.06.013.
National Toxicology Program. Toxicology and carcinogenesis studies of Glycidol (CAS No. 556-52-5) in F344/N rats and B6C3F1 mice (gavage studies). Natl Toxicol Program Tech Rep Ser. 1990;374:1–229.
Oey SB, van der Fels-Klerx HJ, Fogliano V, et al. Mitigation strategies for the reduction of 2-and 3-MCPD esters and Glycidyl esters in the vegetable oil processing industry. Compr Rev Food Sci Food Saf. 2019;18:349–61. https://doi.org/10.1111/1541-4337.12415.
Pudel F, Benecke P, Fehling P, et al. On the necessity of edible oil refining and possible sources of 3-MCPD and glycidyl esters. Eur J Lipid Sci Technol. 2011;113:368–73. https://doi.org/10.1002/ejlt.201000460.
Rietjens I, Michael A, Bolt HM, et al. The role of endogenous versus exogenous sources in the exposome of putative genotoxins and consequences for risk assessment. Arch Toxicol. 2022;96(5):1297–352. https://doi.org/10.1007/s00204-022-03242-0.
Ruenz M, Bakuradze T, Eisenbrand G, et al. Monitoring urinary mercapturic acids as biomarkers of human dietary exposure to acrylamide in combination with acrylamide uptake assessment based on duplicate diets. Arch Toxicol. 2016;90:873–81. https://doi.org/10.1007/s00204-015-1494-9.
Rydberg P, von Stedingk H, Magner J, et al. LC/MS/MS analysis of N-Terminal protein adducts with improved sensitivity: a comparison of selected edman isothiocyanate reagents. Int J Anal Chem. 2009;2009:153472. https://doi.org/10.1155/2009/153472.
Sabbioni G, Day BW. Quo vadis blood protein adductomics? Arch Toxicol. 2022;96:79–103. https://doi.org/10.1007/s00204-021-03165-2.
Shimamura Y, Inagaki R, Honda H, et al. Does external exposure of glycidol-related chemicals influence the forming of the hemoglobin adduct, N-(2,3-dihydroxypropyl)valine, as a biomarker of internal exposure to glycidol? Toxics. 2020;8(4):119. https://doi.org/10.3390/toxics8040119.
Skipper PL, Tannenbaum SR. Protein adducts in the molecular dosimetry of chemical carcinogens. Carcinogenesis. 1990;11:507–18.
Törnqvist M, Mowrer J, Jensen S, et al. Monitoring of environmental cancer initiators through hemoglobin adducts by a modified Edman degradation method. Anal Biochem. 1986;154:255–66.
Törnqvist M, Fred C, Haglund J, et al. Protein adducts: quantitative and qualitative aspects of their formation, analysis and applications. J Chromatogr B Analyt Technol Biomed Life Sci. 2002;778:279–308.
Weikert C, Trefflich I, Menzel J, et al. Vitamin and mineral status in a vegan diet. Dtsch Arztebl Int. 2020;117:575–82. https://doi.org/10.3238/arztebl.2020.0575.
Wollin KM, Bader M, Müller M, et al. Assessment of long-term health risks after accidental exposure using haemoglobin adducts of epichlorohydrin. Toxicol Lett. 2014;231:378–86. https://doi.org/10.1016/j.toxlet.2014.07.020.
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Monien, B.H., Abraham, K. (2023). The Carcinogen Glycidol and Use of N-(2,3-Dihydroxypropyl)-valine in Hemoglobin as a Biomarker of Exposure. In: Patel, V.B., Preedy, V.R., Rajendram, R. (eds) Biomarkers in Toxicology. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Cham. https://doi.org/10.1007/978-3-031-07392-2_65
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