Archives of Toxicology

, Volume 87, Issue 9, pp 1649–1659

Relative oral bioavailability of glycidol from glycidyl fatty acid esters in rats

  • Klaus E. Appel
  • Klaus Abraham
  • Edith Berger-Preiss
  • Tanja Hansen
  • Elisabeth Apel
  • Sven Schuchardt
  • Carla Vogt
  • Nadiya Bakhiya
  • Otto Creutzenberg
  • Alfonso Lampen
Toxicokinetics and Metabolism

DOI: 10.1007/s00204-013-1061-1

Cite this article as:
Appel, K.E., Abraham, K., Berger-Preiss, E. et al. Arch Toxicol (2013) 87: 1649. doi:10.1007/s00204-013-1061-1

Abstract

In order to quantify the relative bioavailability of glycidol from glycidyl fatty acid esters in vivo, glycidyl palmitoyl ester and glycidol were orally applied to rats in equimolar doses. The time courses of the amounts of glycidol binding to hemoglobin as well as the excretion of 2,3-dihydroxypropyl mercapturic acids were determined. The results indicate that glycidol is released from the glycidyl ester by hydrolysis and rapidly distributed in the organism. In relation to glycidol, there was only a small timely delay in the binding to hemoglobin for the glycidol moiety released from the ester which may be certainly attributed to enzymatic hydrolysis. In both cases, however, an analogous plateau was observed representing similar amounts of hemoglobin binding. With regard to the urinary excretion of mercapturic acids, also similar amounts of dihydroxypropyl mercapturic acids could be detected. In an ADME test using a virtual double tag (3H, 14C) of glycidyl palmitoyl ester, a diverging isotope distribution was detected. The kinetics of the 14C-activity reflected the kinetics of free glycidol released after hydrolysis of the palmitoyl ester. In view of this experimental data obtained in rats, it is at present justified for the purpose of risk assessment to assume complete hydrolysis of the glycidyl ester in the gastrointestinal tract. Therefore, assessment of human exposure to glycidyl fatty acid ester should be regarded as an exposure to the same molar quantity of glycidol.

Keywords

Glycidol Glycidyl fatty acid esters Relative bioavailability Kinetics Risk assessment 

Abbreviations

ADME

Absorption, distribution, metabolism and excretion

AUC

Area under the curve

BfR

Federal Institute for Risk Assessment

Bwt

Body weight

diHOPrVal

N-(2,3-dihydroxypropyl)valine

DHPMA

2,3-dihydroxypropyl mercapturic acid or N-acetyl-S(2,3-dihydroxypropyl)cysteine

GC–MS

Gas chromatography-mass spectrometry

HILIC

Hydrophilic interaction liquid chromatography

HPLC

High-performance liquid chromatography

3-MCPD

3-chloropropane-1,2-diol

MRM

Multiple reaction monitoring

MSD

Mass selective detector

NCI

Negative chemical ionization

NTP

National toxicology program

SIM

Single ion monitoring

Supplementary material

204_2013_1061_MOESM1_ESM.doc (57 kb)
Supplementary material 1 (DOC 57 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Klaus E. Appel
    • 1
  • Klaus Abraham
    • 1
  • Edith Berger-Preiss
    • 2
  • Tanja Hansen
    • 2
  • Elisabeth Apel
    • 2
  • Sven Schuchardt
    • 2
  • Carla Vogt
    • 3
  • Nadiya Bakhiya
    • 1
  • Otto Creutzenberg
    • 2
  • Alfonso Lampen
    • 1
  1. 1.Department of Food SafetyFederal Institute for Risk Assessment (BfR)BerlinGermany
  2. 2.Fraunhofer Institute for Toxicology and Experimental MedicineHannoverGermany
  3. 3.Institute for Inorganic ChemistryLeibniz University of HannoverHannoverGermany

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