Abstract

BACKGROUNDBifenthrin is usually considered a Type I pyrethroid, because it lacks an α‐CN group present in Type II pyrethroids, but some previous studies suggest a mixed Type I/II mode‐of‐action. Results are presented for bifenthrin in a rat developmental neurotoxicity (DNT) study along with effects on Na currents in human VGSC subtypes. Molecular modeling comparisons were also made for bifenthrin and other pyrethroids.RESULTSIn a rat DNT study, bifenthrin produced tremors and clonic convulsions in dams and pups and slightly reduced acoustic startle response amplitude, and increased Tmax, at PND20 in females. Similar blood levels of bifenthrin were measured in dams and pups at each dose level i.e. no concentration in pups. In human VGSC experiments, using the Nav1.8 subtype, bifenthrin's effects on inactivation were slight, as for Type II pyrethroids, but without large prolongation of the tail current (deactivation) seen with Type II. Molecular modeling of bifenthrin indicates that the o‐Me group may occupy a similar space to the α‐CN group of cypermethrin and fenpropathrin.CONCLUSIONIn a DNT study and on human Nav1.8 tail currents bifenthrin showed Type I and II effects, similar to some published studies. Overall, bifenthrin acts as a mixed Type I/II pyrethroid. © 2018 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Highlights

  • The synthesis of the first synthetic pyrethroid insecticide, allethrin, was based on the structure of pyrethrin I, a component of pyrethrum extract isolated from Chrysanthemum plants

  • Bifenthrin was evaluated in a rat developmental neurotoxicity (DNT) study and in human voltage-gated sodium channel (VGSC) expressed in Chinese hamster ovary (CHO) cells

  • The combined effects of bifenthrin on Acoustic Startle Response (ASR) amplitude and latency are consistent with Type II vs. Type I pyrethroids

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Summary

Introduction

The synthesis of the first synthetic pyrethroid insecticide, allethrin, was based on the structure of pyrethrin I, a component of pyrethrum extract isolated from Chrysanthemum plants. Starting in the early 1960s, Toshio Narahashi studied the mechanism of action of pyrethroids (allethrin), using giant axons from the cockroach.[2,3]. Giant axons from the squid and crayfish were subsequently studied in efforts to understand the interaction of allethrin with the voltage-gated sodium channel (VGSC).[4–6]. Allethrin reduced sodium ion conductance leading to nerve blockage, whereas at high temperatures, delayed sodium channel inactivation and increased negative after-potential resulted in repetitive firing following electrical stimulation. Results are presented for bifenthrin in a rat developmental neurotoxicity (DNT) study along with effects on Na currents in human VGSC subtypes. Molecular modeling comparisons were made for bifenthrin and other pyrethroids

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