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

Laurence Ribonnet (1) , Edwige van Der Heiden (2) , Ingrid Nobels (3) , Agnès Chaumont (1) , Anne-Sophie Remacle (2) , Sarah de Saeger (4) , Yves-Jacques Schneider (1) , Marie-Louise Scippo (2) , Ronny Blust (2) , Luc Pussemier (5) , Yvan Larondelle (1)

1 Institut des Sciences de la Vie
2 Department of Food Sciences
3 Laboratory of Ecophysiology, Biochemistry and Toxicology
4 Laboratory of Food Analysis
5 CODA-CERVA-VAR

In vitro risk assessment of dietary contaminants has become a priority in human food safety. In the present paper, we propose an in vitro approach associating different complementary tools in an original toolbox aiming at improving 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 estrogenic 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 recovered 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, we 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 estrogen sensitive reporter cell line. All these results are in accordance with literature, suggesting that our 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.

Mots clés: Life Sciences

Laurence Ribonnet, Edwige van Der Heiden, Ingrid Nobels, Agnès Chaumont, Anne-Sophie Remacle, 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, 2011, pp.1. ⟨10.1080/19440049.2011.584069⟩. ⟨hal-00719070⟩