title: In vitro combined cytotoxic effects of pesticide cocktails simultaneously found in the French diet.
abstract: Although human populations may be constantly exposed to complex pesticide mixtures through their diet, the human health risk of pesticide exposure is currently assessed on the basis of toxicity data on individual compounds. To investigate the combined toxic effects of pesticide cocktails previously identified in the French diet, we first studied the cytotoxicity induced by seven cocktails composed of two to six pesticides on human hepatic (HepG2) and colon (Caco-2) cell lines using the MTT and neutral red uptake assays. Secondly, we challenged to assess the combined effects of the two most cytotoxic cocktails by comparing the measured effects of the mixtures with the predictions based on additive effects on two concepts-independent action (IA) and concentration addition (CA). For the cocktail composed of dichlorodiphenyltrichloroethane (DDT) and dieldrin, the cytotoxicity of the equimolar cocktail proved greater than the additive effect estimated by the two concepts. Furthermore, apoptosis induction was higher in equimolar cocktail than predicted by summing the effects of DDT and dieldrin. Thus, some supra-additive toxicity was found in the DDT-dieldrin cocktail. Nevertheless, if IA and CA models could reveal combined effects of pesticide cocktails, an accurate evaluation remains challenging.
authors.affiliation: ANSES, French Agency for Food, Environmental and Occupational Health & Safety, Fougères Laboratory, Toxicology Contaminants Unit, Fougères, France. natsuko.takakura-mikogami@anses.fr
authors.forename: Natsuko
authors.initials: N
authors.lastname: Takakura
authors.forename: Pascal
authors.initials: P
authors.lastname: Sanders
authors.forename: Valérie
authors.initials: V
authors.lastname: Fessard
authors.forename: Ludovic
authors.initials: L
authors.lastname: Le Hégarat
mesh_terms: D018938:Caco-2 Cells / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002460:Cell Line / Q000187:drug effects; D003634:DDT / Q000633:toxicity; D004026:Dieldrin / Q000633:toxicity; D005247:Feeding Behavior; D005506:Food Contamination; D005602:France; D006801:Humans; D008962:Models, Theoretical; D010575:Pesticides / Q000032:analysis / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018570:Risk Assessment
chemical_list: D010575:Pesticides; D017382:Reactive Oxygen Species; D003634:DDT; D053148:Caspase 3; D053179:Caspase 7; D004026:Dieldrin