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Relative oral bioavailability of 3-MCPD from 3-MCPD fatty acid esters in rats

  • Toxicokinetics and Metabolism
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Abstract

In order to quantify the relative oral bioavailability of 3-chloropropane-1,2-diol (3-MCPD) from 3-MCPD fatty acid diesters in vivo, 1,2-dipalmitoyl-3-chloropropane-1,2-diol (3-MCPD diester) and 3-MCPD were orally applied to rats in equimolar doses. In both cases, the time courses of 3-MCPD concentrations were measured in blood, various organs, tissues and intestinal luminal contents. The results show that 3-MCPD is released by enzymatic hydrolysis from the 3-MCPD diester in the gastrointestinal tract and distributed to blood, organs and tissues. Based on the measurements in blood, the areas under the curve (AUC) for 3-MCPD were calculated. By comparing both AUC, the relative amount of 3-MCPD bioavailable from the 3-MCPD diester was calculated to be 86 % on average of the amount bioavailable following administration of 3-MCPD. In view of limited experimental data, it is justified for the purpose of risk assessment to assume complete hydrolysis of the diesters in the gastro-intestinal tract. Therefore, assessment of the extent of exposure to 3-MCPD released from its fatty acid esters should be performed in the same way as exposure to the same molar quantity of 3-MCPD.

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Abbreviations

3-MCPD:

3-Chloropropane-1,2-diol

3-MCPD diester:

1,2-Dipalmitoyl-3-chloropropane-1,2-diol

MTBE:

Methyl tert-butyl ether

HFBA:

Heptafluorobutyric acid anhydride

AUC:

Area under the curve

BMD:

Benchmark dose

TDI:

Tolerable daily intake

LOAEL:

Lowest observed adverse effect level

EFSA:

European Food Safety Authority

mg/kg b.w.:

Milligram/kilogram body weight

Fraunhofer ITEM:

Fraunhofer Institute for Toxicology and Experimental Medicine

BfR:

Federal Institute for Risk Assessment

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Acknowledgments

This work was financially supported by the German Federal Ministry of Food, Agriculture and Consumer Protection (BMELV) through the Federal Office for Agriculture and Food (BLE), grant number 514-06.01-2808HS013. The contributions made by Dr. Susanne Andres and Dr. Nadiya Bakhiya for the discussion are gratefully acknowledged.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Food Safety, Federal Institute for Risk Assessment, Max-Dohrn-Strasse 8-10, 10589, Berlin, Germany

    Klaus Abraham, Klaus E. Appel & Alfonso Lampen

  2. Department of Chemical Safety, Federal Institute for Risk Assessment, Max-Dohrn-Strasse 8-10, 10589, Berlin, Germany

    Hans Mielke

  3. Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Strasse 1, 30625, Hannover, Germany

    Edith Berger-Preiss, Elisabeth Apel, Susanne Gerling & Otto Creutzenberg

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  1. Klaus Abraham
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  2. Klaus E. Appel
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  3. Edith Berger-Preiss
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  4. Elisabeth Apel
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Correspondence to Klaus E. Appel.

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Abraham, K., Appel, K.E., Berger-Preiss, E. et al. Relative oral bioavailability of 3-MCPD from 3-MCPD fatty acid esters in rats. Arch Toxicol 87, 649–659 (2013). https://doi.org/10.1007/s00204-012-0970-8

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  • DOI: https://doi.org/10.1007/s00204-012-0970-8

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