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Estimation of the Intestinal Absorption and Metabolism Behaviors of 2- and 3-Monochloropropanediol Esters

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Lipids

Abstract

The regioisomers of the di- and mono-oleate of monochloropropanediol (MCPD) have been synthesized and subsequently hydrolyzed with pancreatic lipase and pancreatin to estimate the intestinal digestion and absorption of these compounds after their intake. The hydrolysates were analyzed by HPLC using a corona charged aerosol detection system, which allowed for the separation and detection of the different regioisomers of the MCPD esters. The hydrolysates were also analyzed by GC–MS to monitor the free MCPD. The results indicated that the two acyl groups of 2-MCPD-1,3-dioleate were smoothly hydrolyzed by pancreatic lipase and pancreatin to give free 2-MCPD. In contrast, the hydrolysis of 3-MCPD-1,2-dioleate proceeded predominantly at the primary position to produce 3-MCPD-2-oleate. 2-MCPD-1-oleate and 3-MCPD-1-oleate were further hydrolyzed to free 2- and 3-MCPD by pancreatic lipase and pancreatin, although the hydrolysis of 3-MCPD-2-oleate was 80 % slower than that of 3-MCPD-1-oleate. The intestinal absorption characteristics of these compounds were evaluated in vitro using a Caco-2 cell monolayer. The results revealed that the MCPD monooleates, but not the MCPD dioleates, were hydrolyzed to produce the free MCPD in the presence of the Caco-2 cells. The resulting free MCPD permeated the Caco-2 monolayer most likely via a diffusion mechanism because their permeation profiles were independent of the dose. Similar permeation profiles were obtained for 2- and 3-MCPDs.

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Abbreviations

MCPD:

Monochloropropanediol

HPLC:

High-performance lipid chromatography

GC–MS:

Gas chromatography mass spectrometry

t-BME:

tert-Butyl methyl ether

Tris:

Tris-(hydroxymethyl)-aminomethane

3-MCPD-d 5 :

3-Monochloropropanediol-deuterated

DMEM:

Dulbecco’s modified Eagle’s medium

EDTA:

Ethylenediaminetetraacetic acid

TEER:

Transepithelial electrical resistance

HBSS:

Hank’s balanced salt solution

CAD:

Corona charged aerosol detection

FFA:

Free fatty acid

References

  1. International Agency for Research on Cancer (IARC) Monographs on the evaluation of carcinogenic risks to humans, IARC (2015) List of classifications, vol 1–114. http://monographs.iarc.fr/index.php. Accessed 29 Oct 2015

  2. Food Additives Series: 48; WHO: Geneva, Switzerland, 2002; http://www.inchem.org/documents/jecfa/jecmono/v48je18.htm. Accessed 12 Feb 2016

  3. Andres S, Appel KE, Lampen A (2013) Toxicology, occurrence and risk characterisation of the chloropropanols in food: 2-monochloro-1,3-propanediol, 1,3-dichloro-2-propanol and 2,3-dichloro-1-propanol. Food Chem Toxicol 58:467–478

    Article  CAS  PubMed  Google Scholar 

  4. Bakhiya N, Abraham K, Gurtler R, Appel KE, Lampen A (2011) Toxicological assessment of 3-chloropropane-1,2-diol and glycidol fatty acid esters in food. Mol Nutr Food Res 55:509–521

    Article  CAS  PubMed  Google Scholar 

  5. Kuhlmann J (2011) Determination of bound 2,3-epoxy-1-propanol (glycidol) and bound monochloropropanediol (MCPD) in refined oils. Eur J Lipid Sci Technol 113:335–344

    Article  CAS  Google Scholar 

  6. MacMahon S, Begley TH, Diachenko GW (2013) Occurrence of 3-MCPD and glycidyl esters in edible oils in the United States. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 30(12):2081–2092

    Article  CAS  PubMed  Google Scholar 

  7. Duboisa M, Tarresa A, Goldmanna T, Emplb AM, Donaubauerb A, Seefeldera W (2012) Comparison of indirect and direct quantification of esters of monochloropropanediol in vegetable oil. J Chromatogr A 1236:189–201

    Article  Google Scholar 

  8. Shimizu M, Vosmann K, Matthäus B (2012) Generation of 3-monochloro-1,2-propanediol and related materials from tri-, di-, and monoolein at deodorization temperature. Eur J Lipid Sci Technol 113:335–344

    Google Scholar 

  9. Ermacora A, Hrncirik K (2014) Influence of oil composition on the formation of fatty acid esters of 2-chloropropane-1,3-diol (2-MCPD) and 3-chloropropane-1,2-diol (3-MCPD) under conditions simulating oil refining. Food Chem 161:383–389

    Article  CAS  PubMed  Google Scholar 

  10. Abraham K, Appel KE, Berger-Preiss E, Apel E, Gerling S, Mielke H, Creutzenberg O, Lampen A (2013) Relative oral bioavailability of 3-MCPD from 3-MCPD fatty acid esters in rats. Arch Toxicol 87:649–659

    Article  CAS  PubMed  Google Scholar 

  11. EFSA scientific report (2011) Comparison between 3-MCPD and its palmitic esters in a 90-day toxicological study. http://www.efsa.europa.eu/en/supporting/doc/187e.pdf. Accessed 29 Oct 2015

  12. Seefelder W, Varga N, Studer A, Williamson G, Scanlan FP, Stadler RH (2008) Esters of 3-chloro-1,2-propanediol (3-MCPD) in vegetable oils: significance in the formation of 3-MCPD. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 25:391–400

    Article  CAS  PubMed  Google Scholar 

  13. Artursson P, Karlsson J (1991) Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells. Biochem Biophys Res Comm 175(3):880–885

    Article  CAS  PubMed  Google Scholar 

  14. Murota K, Shimizu S, Miyamoto S, Izumi T, Obata A, Kikuchi M, Terao J (2002) Unique uptake and transport of isoflavone aglycones by human intestinal Caco-2 cells: comparison of isoflavonoids and flavonoids. J Nutr 132(7):1956–1961

    CAS  PubMed  Google Scholar 

  15. Buhrke T, Weisshaar R, Lampen A (2011) Absorption and metabolism of the food contaminant 3-chloro-1,2-propanediol (3-MCPD) and its fatty acid esters by human intestinal Caco-2 cells. Arch Toxicol 85:1201–1208

    Article  CAS  PubMed  Google Scholar 

  16. Buhrke T, Frenzel F, Kuhlmann J, Lampen A (2015) 2-Chloro-1,3-propanediol (2-MCPD) and its fatty acid esters: cytotoxicity, metabolism, and transport by human intestinal Caco-2 cells. Arch Toxicol 89(12):2243–2251

    Article  CAS  PubMed  Google Scholar 

  17. Kaze N, Sato H, Yamamoto H, Watanabe Y (2011) Bidirectional conversion between 3-monochloro-1,2-propanediol and glycidol in course of the procedure of DGF standard methods. J Am Oil Chem Soc 88:1143–1151

    Article  CAS  Google Scholar 

  18. Sato H, Kaze N, Yamamoto H, Watanabe Y (2013) 2-Monochloro-1,3-propanediol (2-MCPD) dynamics in DGF standard methods and quantification of 2-MCPD. J Am Oil Chem Soc 90:1121–1130

    Article  CAS  Google Scholar 

  19. Deutsche Gesellschaft für Fettwissenschaft, DGF Standard Methods Section C-Fats C-VI 18 (10) (2011) Fatty-acid-bound 3-chloropropane-1,2-diol (3-MCPD) and 2,3-epoxipropane-1-ol (glycidol) Determination in oils and fats by GC/MS (Differential measurement)

  20. Scientific Report of EFSA (2013) Analysis of occurrence of 3-monochloropropane-1,2-diol (3-MCPD) in food in Europe in the years 2009–2011 and preliminary exposure assessment. http://www.efsa.europa.eu/sites/default/files/scientific_output/files/main_documents/3381.pdf. Accessed 29 Oct 2015

  21. Onami S, Cho YM, Toyoda T, Horibata K, Ishii Y, Umemura T, Honma M, Nohmi T, Nishikawa A, Ogawa K (2014) Absence of in vivo genotoxicity of 3-monochloropropane-1,2-diol and associated fatty acid esters in a 4-week comprehensive toxicity study using F344 gpt delta rats. Mutagenesis 29(4):295–302

    Article  CAS  PubMed  Google Scholar 

  22. Onami S, Cho YM, Toyoda T, Mizuta Y, Yoshida M, Nishikawa A, Ogawa K (2014) A 13-week repeated dose study of three 3-monochloropropane-1,2-diol fatty acid esters in F344 rats. Arch Toxicol 88(4):871–880

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank Mr, Shun Kumamoto of Tsuji Oil Mills Co., Ltd., Ms. Sayaka Azuma and Ms. Hitomi Matsui of Ueda Oils and Fats MFG. Co., Ltd. for their technical support. This work was supported by JSPS KAKENHI grant number 25450197.

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Authors and Affiliations

  1. Ueda Oils and Fats MFG Co. Ltd, 17 Uozakihamamachi, Higashinada-ku, Kobe, 658-0024, Japan

    Naoki Kaze & Hiroshi Yamamoto

  2. Osaka Municipal Technical Research Institute, 1-6-50 Morinomiya, Joto-ku, Osaka, 536-8553, Japan

    Yomi Watanabe & Hirofumi Sato

  3. Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1 Kowakae, Higashiosaka, Osaka, 577-8502, Japan

    Kaeko Murota

  4. Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka, 599-8531, Japan

    Miyako Kotaniguchi & Shinichi Kitamura

  5. Department of Nutrition, Osaka Prefecture University, Habikino, Osaka, 583-8555, Japan

    Hiroshi Inui

  6. Center for Research and Development of Bioresources, Osaka Prefecture University, 1-2, Gakuen-cho, Naka-ku, Sakai, Osaka, 599-8570, Japan

    Hiroshi Inui

Authors
  1. Naoki Kaze
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  2. Yomi Watanabe
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  3. Hirofumi Sato
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Correspondence to Yomi Watanabe.

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Electronic Supplementary Material

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11745_2016_4143_MOESM1_ESM.pdf

Supplementary material 1 Figure 1: Permeabilities of the 2- and 3-MCPD-monooleates as determined using Caco-2 cells. The conditions for the transport experiments were the same as those described in Fig. 7, except the concentrations of 2- and 3-MCPD monooleate were increased from 0.1 to 1.0 mM, and using Transwell inserts in the presence or in the absence of Caco-2 cell monolayer. a, filled triangle, 2-MCPD-1-oleate-apical; filled circle, 2-MCPD-apical; open triangle, 2-MCPD-basolateral; open diamond, 2-MCPD-cell. b and c, filled triangle, 3-MCPD-1-oleate-apical; filled diamond, 3-MCPD-2-oleate-apical; filled circle, 3-MCPD-apical; open triangle, 3-MCPD-basolateral; open diamond, 3-MCPD-cell. d, 2-MCPD-1-oleate-apical in the presence (filled triangle) and in the absence (open square) of Caco-2 cell monolayer. e, 3-MCPD-1-oleate-apical in the presence (filled triangle) and in the absence (open square) of Caco-2 cell monolayer. f, 3-MCPD-2-oleate-apical in the presence (filled diamond) and in the absence (open square) of Caco-2 cell monolayer (PDF 74 kb)

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Kaze, N., Watanabe, Y., Sato, H. et al. Estimation of the Intestinal Absorption and Metabolism Behaviors of 2- and 3-Monochloropropanediol Esters. Lipids 51, 913–922 (2016). https://doi.org/10.1007/s11745-016-4143-z

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