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Mixture Risk Assessment of Atrazine, Chlorpyrifos and Endosulfan

Ahmad Nawaz, George De Sousa and Roger Rahmani, INRA, France

During the last decades there has been increasing focus on the fact that humans are concurrently exposed to a number of chemicals via food and environment. The risk assessment of pesticide residues in food is based on toxicological evaluation of the single compounds and no internationally accepted procedure exists to evaluate cumulative exposure to multiple residues of pesticides in crops, except for a few groups of pesticides sharing a group ADI. The chemicals may have a combined action that causes a lower or higher toxic effect than would be expected from knowledge about the single compounds. We analysed the cytotoxicity of the cocktail of three pesticides (Endosulfan-E, Chlorpyrifos-C, Atrazine-A) in human and rat hepatocytes primary cultures (fresh and cryopreserved) through an innovative real time cellular impedance method (Electronic Sensor Technology). The results indicate that the pesticide’s mixture is more cytotoxic as compared to the binary combinations and the individual compounds. The binary mixture of Endosulfan and Chlorpyrifos shows a synergistic effect. Atrazine alone seems to be non-toxic even at highest concentration of 100µM. The ability of pesticides to activate the Pregnane X Receptor (PXR) was tested by monitoring luciferase activities in a stably transfected hPXR/HepG2 cell line, which was exposed to the various pesticides and combinations. ACE mixture showed the highest induction (around 18-fold) followed by EC (17-fold) at 10µM. As PXR regulates cell detoxication activities, in particular CYP3A4 one, these pesticides may impact pharmaco-toxicokinetics of xenobiotic agents.

(presenting author: Ahmad Nawaz)

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