Pyrethroid neurotoxicity studies with bifenthrin indicate a mixed Type I/II mode of action

• Published in: Pest management science 2019-04, Vol.75 (4), p.1190-1197
• Main Authors: Gammon, Derek W, Liu, Zhiwei, Chandrasekaran, Appavu, El‐Naggar, Shaaban F, Kuryshev, Yuri A, Jackson, Sharon
• Format: Article
• Language: English
• Subjects: Acoustic startle response; bifenthrin; Blood levels; Convulsions; Cypermethrin; Deactivation; Females; Inactivation; Insecticides; ion channels; Mode of action; Modelling; Molecular modelling; Neurotoxicity; Organic chemistry; Pest control; Prolongation; Pyrethroids; Sodium channels (voltage-gated); Startle response; Studies; Tremors; Type I and II; voltage‐gated Sodium Channel
• ISSN: 1526-498X; 1526-4998
• DOI: 10.1002/ps.5300

BACKGROUND Bifenthrin 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. RESULTS In 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. CONCLUSION In 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. Bifenthrin was previously considered a Type I pyrethroid. However, data presented here, including a rat DNT study and one on patch‐clamped human VGSCs, indicate mixed Type I and II properties.