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Bifenthrin inhibits neurite outgrowth in differentiating PC12 cells.

Van Tran, Natalie Hoffman, Adaobi Mofunanaya, Stephen Pryor, Olutosin Ojugbele, Ashlea McLaughlin, Lydia Gibson, Josephine A. Bonventre, Katherine Flynn, Benjamin Weeks

Med Sci Monit 2006; 12(2): BR57-62

ID: 445228

Available online: 2006-02-01

Published: 2006-02-01

Background: Bifenthrin is a third generation member of the synthetic pyrethroidfamily of insecticides. As a new pesticide within a relatively new class of pesticides, bifenthrin isconsidered relatively safe. Here, we used the PC12 neuronal cell line to examine the effect of bifenthrinon the formation of neurites and the potential developmental neurotoxicity of this pesticide. Material/Methods:PC12 cells were exposed to varying concentrations of technical grade bifenthrin or Ortho Home Defense[sup]®[/sup].Cell viability was determined using the AlmarBlue Toxicity Assay. Nontoxic concentrations of these chemicalswere concomitantly with nerve growth factor and neurite outgrowth was assessed. Results: Ortho Home Defense[sup]®[/sup]preparation reduced PC12 cell viability by approximately 50% and 70% at dilutions that correlate to bifenthrinconcentrations of 10[sup]-5[/sup] M and 10[sup]®[/sup] M, respectively. In contrast, technical grade bifenthrin, was nottoxic to PC12 cells at 10[sup]-3[/sup] M, which was the highest concentration tested that was soluble. At "nontoxic"concentrations of 10[sup]-7[/sup] M and 10[sup]-6[/sup] M, the Ortho Home Defense[sup]®[/sup] inhibited nerve growth factor-mediatedneurite outgrowth by 30% and 55% respectively. Furthermore the nontoxic concentrations of technical gradebifenthrin of 10[sup]-6[/sup] M and 10[sup]-3[/sup] M inhibited neurite outgrowth by approximately 35% and 75% respectively.Conclusions: These data suggest that the toxicity of the Ortho Home Defense[sup]®[/sup] preparation was dueto the "inert" additives in the preparation and not the bifenthrin itself. Further, these data suggestthat, even in the absence of overt toxicity, bifenthrin may have deleterious effects to developing nervoussystem.

Keywords: Cell Differentiation, Animals, Cell Survival - drug effects, Insecticides - toxicity, Neurites - pathology, Neurotoxins - toxicity, PC12 Cells, Pyrethrins - toxicity, Rats