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

Abstract

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.

Insight Into Microbial Applications for the Biodegradation of Pyrethroid Insecticides

“…Pyrethroids are neurotoxic pesticides and affect neurotransmitters (Gammon et al, 2019). Effect of low acute oral dose of pyrethroids has been investigated in small rodents.…”

“…Pyrethroids are the most commonly used global pesticides. Chrysanthemum cinerariaefolium flowers are the natural source of pyrethroids and allethrin was developed as the first synthetic pyrethroid insecticide in 1949 (Ensley, 2018; Gammon et al, 2019; Xu et al, 2019). Pyrethroids can be divided into two groups, type I pyrethroids containing basic cyclopropane carboxylic (e.g., allethrin) and type II pyrethroids containing cyano group (Proudfoot, 2005; Wolansky and Harrill, 2008; Chang et al, 2016; Figure 1).…”

“…Pyrethroids are reported to be 2250 times more toxic to insect than mammals and disrupt sodium, chloride channels (Chrustek et al, 2018). At high concentrations pyrethroids inhibit the functioning of gamma amino butyric acid (GABA) gated chloride ion channel (Bradberry et al, 2005; Gammon et al, 2019). Pyrethroids are mainly used to control insect pests of agriculture, horticulture, forestry and household.…”

“…Bio-absorption of pyrethroids was detected in the urine samples of outdoor workers in California (Sullivan et al, 2019), which indicates the importance of this topic. In rats, the developmental of bifenthrin neurotoxicity was reported as mixed type (typeI/II) (Gammon et al, 2019) whereas non-target neurotoxicity of pyrethroids has also been investigated in zebrafish (Paravani et al, 2017; Awoyemi et al, 2019; Strungaru et al, 2019).…”

The history of extensive structural modifications of pyrethroids

“…However, several studies have suggested that it acts as a mixture of Type I and Type II pyrethroids. 55) Another remarkable application of fluorine chemistry to pyrethroids involved polyfluorobenzyl esters (Fig. 10).…”