Advanced search
1 file | 703.78 KB

Potential of an in vitro toolbox combined with exposure data as a first step for the risk assessment of dietary chemical contaminants

Author
Organization
Abstract
In vitro risk assessment of dietary contaminants has become a priority in human food safety. This paper proposes an in vitro approach associating different complementary tools in an original toolbox and aims to improve the assessment of the toxicological impact of dietary contaminants at realistic human exposure levels, with a special focus on the intestinal compartment. The system is based on the use of four complementary cellular tools, namely stress gene induction in transgenic strains of Escherichia coli, modulation of the activity of key biotransformation enzymes (cytochrome P-450 (CYP) 1A1 and 3A4) in a human intestinal cell line, and activation of aryl hydrocarbon receptor (AhR) and oestrogenic receptor (ER)-dependent genes in agonistic and antagonistic assays with luciferase reporter cells. It was applied to four chosen model molecules: ochratoxin A (OTA) and deoxynivalenol (DON), two common food-borne mycotoxins, and imazalil (IMA) and benomyl (BEN), two fungicides widely occurring in foodstuffs. All these assays were performed at or around a realistic intestinal concentration, determined through a deterministic approach based on the calculation of a theoretical maximum daily intake (TMDI). Using the four model molecules, it is clearly highlighted that induction of CYP1A1 activity and inhibition of CYP3A4 activity occurred in Caco-2 cells at a realistic intestinal concentration of IMA. Furthermore, some bacterial stress genes were induced in a range of realistic concentrations, following exposure to DON and IMA. In addition, BEN clearly provoked an ER agonistic activity in a human oestrogen sensitive reporter cell line. All these results are in accordance with the literature, suggesting that the in vitro toolbox constitutes an interesting approach in order to obtain a first 'fingerprint' of dietary contaminants at realistic human exposure for further risk assessment.
Keywords
ARYL-HYDROCARBON RECEPTOR, TRANS-RETINOIC ACID, pesticide residues, mycotoxins, microbial screening, cytotoxicity, toxicology, receptors, INTESTINAL CACO-2 CELLS, bioassay, HUMAN CYTOCHROME-P450 ISOFORMS, BALKAN ENDEMIC NEPHROPATHY, PREGNANE-X-RECEPTOR, ESTROGEN-RECEPTOR, OCHRATOXIN-A, CYP1A1 INDUCTION, PHYSIOLOGICAL FUNCTIONS

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 703.78 KB

Citation

Please use this url to cite or link to this publication:

Chicago
Ribonnet, L, E van der Heiden, I Nobels, A Chaumont, A-S Remacle, Sarah De Saeger, Y-J Schneider, et al. 2011. “Potential of an in Vitro Toolbox Combined with Exposure Data as a First Step for the Risk Assessment of Dietary Chemical Contaminants.” Food Additives and Contaminants Part A-chemistry Analysis Control Exposure & Risk Assessment 28 (9): 1136–1158.
APA
Ribonnet, L., van der Heiden, E., Nobels, I., Chaumont, A., Remacle, A.-S., De Saeger, S., Schneider, Y.-J., et al. (2011). Potential of an in vitro toolbox combined with exposure data as a first step for the risk assessment of dietary chemical contaminants. FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT, 28(9), 1136–1158.
Vancouver
1.
Ribonnet L, van der Heiden E, Nobels I, Chaumont A, Remacle A-S, De Saeger S, et al. Potential of an in vitro toolbox combined with exposure data as a first step for the risk assessment of dietary chemical contaminants. FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT. 2011;28(9):1136–58.
MLA
Ribonnet, L, E van der Heiden, I Nobels, et al. “Potential of an in Vitro Toolbox Combined with Exposure Data as a First Step for the Risk Assessment of Dietary Chemical Contaminants.” FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT 28.9 (2011): 1136–1158. Print.
@article{1976920,
  abstract     = {In vitro risk assessment of dietary contaminants has become a priority in human food safety. This paper proposes an in vitro approach associating different complementary tools in an original toolbox and aims to improve the assessment of the toxicological impact of dietary contaminants at realistic human exposure levels, with a special focus on the intestinal compartment. The system is based on the use of four complementary cellular tools, namely stress gene induction in transgenic strains of Escherichia coli, modulation of the activity of key biotransformation enzymes (cytochrome P-450 (CYP) 1A1 and 3A4) in a human intestinal cell line, and activation of aryl hydrocarbon receptor (AhR) and oestrogenic receptor (ER)-dependent genes in agonistic and antagonistic assays with luciferase reporter cells. It was applied to four chosen model molecules: ochratoxin A (OTA) and deoxynivalenol (DON), two common food-borne mycotoxins, and imazalil (IMA) and benomyl (BEN), two fungicides widely occurring in foodstuffs. All these assays were performed at or around a realistic intestinal concentration, determined through a deterministic approach based on the calculation of a theoretical maximum daily intake (TMDI). Using the four model molecules, it is clearly highlighted that induction of CYP1A1 activity and inhibition of CYP3A4 activity occurred in Caco-2 cells at a realistic intestinal concentration of IMA. Furthermore, some bacterial stress genes were induced in a range of realistic concentrations, following exposure to DON and IMA. In addition, BEN clearly provoked an ER agonistic activity in a human oestrogen sensitive reporter cell line. All these results are in accordance with the literature, suggesting that the in vitro toolbox constitutes an interesting approach in order to obtain a first 'fingerprint' of dietary contaminants at realistic human exposure for further risk assessment.},
  author       = {Ribonnet, L and van der Heiden, E and Nobels, I and Chaumont, A and Remacle, A-S and De Saeger, Sarah and Schneider, Y-J and Scippo, M-L and Blust, R and Pussemier, L and Larondelle, Y},
  issn         = {1944-0049},
  journal      = {FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE \& RISK ASSESSMENT},
  keyword      = {ARYL-HYDROCARBON RECEPTOR,TRANS-RETINOIC ACID,pesticide residues,mycotoxins,microbial screening,cytotoxicity,toxicology,receptors,INTESTINAL CACO-2 CELLS,bioassay,HUMAN CYTOCHROME-P450 ISOFORMS,BALKAN ENDEMIC NEPHROPATHY,PREGNANE-X-RECEPTOR,ESTROGEN-RECEPTOR,OCHRATOXIN-A,CYP1A1 INDUCTION,PHYSIOLOGICAL FUNCTIONS},
  language     = {eng},
  number       = {9},
  pages        = {1136--1158},
  title        = {Potential of an in vitro toolbox combined with exposure data as a first step for the risk assessment of dietary chemical contaminants},
  url          = {http://dx.doi.org/10.1080/19440049.2011.584069},
  volume       = {28},
  year         = {2011},
}

Altmetric
View in Altmetric
Web of Science
Times cited: