title: Evidence for dose-additive effects of a type II pyrethroid mixture. In vitro assessment.
abstract: Despite the widespread use of pyrethroid insecticides that led to common exposure in the population, few studies have been conducted to quantitatively assess dose-additive effects of pyrethroids using a funcional measure involved in the common toxic mode of action. The aim of this study was to evaluate the potency and efficacy of 6 Type II pyretroids (α-cypermethrin, cyfluthrin, λ-cyhalothrin, deltamethrin, cyphenothrin and esfenvalerate) to evoke induction of both nitric oxide and lipid peroxides levels measured as malondialdehyde in three in vitro models (SH-SY5Y, HepG2 and Caco-2 human cells) as well as to test the hypothesis of dose additivity for mixtures of these same 6 pyrethroids. Concentration-responses for 6 pyrethroids were determined as well as the response to mixtures of all 6 pyrethroids. Additivity was tested assuming a dose-additive model. The human neuroblastoma SH-SY5Y cell line was the most sensitive in vitro model. The rank order of potency for cell SH-SY5Y viability MTT assay was deltamethrin>cyphenothrin>λ-cyhalothrin>cyfluthrin>esfenvalerate>α-cypermethrin. When 6 pyrethroids were present in the mixture at an equitoxic mixing ratio, the action on nitric oxide (NO) and lipid peroxides measured as malondialdehyde (MDA) production was consistent with a dose-additive model. The results of the present study are consistent with previous reports of additivity of pyrethroids in vivo e in vitro.
authors: Departamento de Toxicología y Farmacología, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain. Electronic address: manarome@ucm.es.
authors: A
authors: A
authors: Romero
authors: Departamento de Toxicología y Farmacología, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain. Electronic address: irmaal@vet.ucm.es.
authors: I
authors: I
authors: Ares
authors: Departamento de Toxicología y Farmacología, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain. Electronic address: eva.ramos@vet.ucm.es.
authors: E
authors: E
authors: Ramos
authors: Departamento de Toxicología y Farmacología, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain. Electronic address: victorc@vet.ucm.es.
authors: V
authors: V
authors: Castellano
authors: Departamento de Toxicología y Farmacología, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain. Electronic address: mmartine@vet.ucm.es.
authors: M
authors: M
authors: Martínez
authors: Departamento de Toxicología y Farmacología, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain. Electronic address: mrml@vet.ucm.es.
authors: M R
authors: MR
authors: Martínez-Larrañaga
authors: Departamento de Toxicología y Farmacología, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain. Electronic address: anadon@vet.ucm.es.
authors: A
authors: A
authors: Anadón
authors: Departamento de Toxicología y Farmacología, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain. Electronic address: arantxam@vet.ucm.es.
authors: M A
authors: MA
authors: Martínez
mesh_terms: D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D056945:Hep G2 Cells; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D008054:Lipid Peroxides / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D011722:Pyrethrins / Q000633:toxicity*
chemical_list: D004785:Environmental Pollutants; D007306:Insecticides; D008054:Lipid Peroxides; D011722:Pyrethrins; D009569:Nitric Oxide
keywords: Additivity; Cytotoxicity; Mixture; Oxidative stress; Type II pyrethroids