Evidence for a separate mechanism of toxicity for the Type I and the Type II pyrethroid insecticides

Charles B. Breckenridge; Larry Holden; Nicholas Sturgess; Myra Weiner; Larry Sheets; Dana Sargent; David M. Soderlund; Jin Sung Choi; Steve Symington; J. Marshall Clark; Steve Burr; David Ray

doi:10.1016/j.neuro.2009.09.002

Evidence for a separate mechanism of toxicity for the Type I and the Type II pyrethroid insecticides

Charles B. Breckenridge
, Larry Holden
, Nicholas Sturgess
, Myra Weiner
, Larry Sheets
, Dana Sargent
, David M. Soderlund
, Jin Sung Choi
, Steve Symington
, J. Marshall Clark
, Steve Burr
, David Ray

Pharmacy

Syngenta
Sielken & Associates, Inc.
TOXpertise, LLC
Bayer AG
Cornell University
Salve Regina University
University of Massachusetts
University of Nottingham

Research output: Contribution to journal › Article › peer-review

191 Scopus citations

Abstract

Neurotoxicity and mechanistic data were collected for six α-cyano pyrethroids (β-cyfluthrin, cypermethrin, deltamethrin, esfenvalerate, fenpropathrin and λ-cyhalothrin) and up to six non-cyano containing pyrethroids (bifenthrin, S-bioallethrin [or allethrin], permethrin, pyrethrins, resmethrin [or its cis-isomer, cismethrin] and tefluthrin under standard conditions. Factor analysis and multivariate dissimilarity analysis were employed to evaluate four independent data sets comprised of (1) fifty-six behavioral and physiological parameters from an acute neurotoxicity functional observatory battery (FOB), (2) eight electrophysiological parameters from voltage clamp experiments conducted on the Na_v1.8 sodium channel expressed in Xenopus oocytes, (3) indices of efficacy, potency and binding calculated for calcium ion influx across neuronal membranes, membrane depolarization and glutamate released from rat brain synaptosomes and (4) changes in chloride channel open state probability using a patch voltage clamp technique for membranes isolated from mouse neuroblastoma cells. The pyrethroids segregated into Type I (T-syndrome-tremors) and Type II (CS syndrome-choreoathetosis with salivation) groups based on FOB data. Of the α-cyano pyrethroids, deltamethrin, λ-cyhalothrin, cyfluthrin and cypermethrin arrayed themselves strongly in a dose-dependent manner along two factors that characterize the CS syndrome. Esfenvalerate and fenpropathrin displayed weaker response profiles compared to the non-cyano pyrethroids. Visual clustering on multidimensional scaling (MDS) maps based upon sodium ion channel and calcium influx and glutamate release dissimilarities gave similar groupings. The non-cyano containing pyrethroids were arrayed in a dose-dependent manner along two different factors that characterize the T-syndrome. Bifenthrin was an outlier when MDS maps of the non-cyano pyrethroids were based on sodium ion channel characteristics and permethrin was an outlier when the MDS maps were based on calcium influx/glutamate release potency. Four of six α-cyano pyrethroids (λ-cyfluthrin, cypermethrin, deltamethrin and fenpropathrin) reduced open chloride channel probability. The R-isomers of λ-l-cyhalothrin reduced open channel probability whereas the S-isomers, antagonized the action of the R-isomers. None of the non-cyano pyrethroids reduced open channel probability, except bioallethrin, which gave a weak response. Overall, based upon neurotoxicity data and the effect of pyrethroids on sodium, calcium and chloride ion channels, it is proposed that bioallethrin, cismethrin, tefluthrin, bifenthrin and permethrin belong to one common mechanism group and deltamethrin, λ-cyhalothrin, cyfluthrin and cypermethrin belong to a second. Fenpropathrin and esfenvalerate occupy an intermediate position between these two groups.

Original language	English
Pages (from-to)	S17-S31
Journal	NeuroToxicology
Volume	30
Issue number	SUPPL.
DOIs	https://doi.org/10.1016/j.neuro.2009.09.002
State	Published - Nov 2009

Bibliographical note

Funding Information:
This research was sponsored by the Pyrethroid Working Group, a trade association of manufacturers of commercial pyrethroid pesticides registered in the United States. Member companies include Amvac, BayerCropScience, Cheminova, Dupont, FMC Corporation, Syngenta, Valent USA Corporation. This work was presented in part at the 2006 Society of Toxicology meeting: Breckenridge C., Holden L., Sheets L., Creek M., Mullen L., Sargent D., Sharp J., Weiner M.L. Principal components and factor analysis of the functional observational battery of 12 pyrethroids. The Toxicologist 2006;90(10):50.

Funding Information:
Charles Breckenridge is employed by Syngenta, a basic manufacturer of λ-cyhalothrin, cypermethrin, permethrin, tefluthrin. These chemicals were evaluated in this study. All work on this paper by Sielken and Associates with the Pyrethroid Working Group, Wilmington, DE, USA. Myra Weiner is a former employee of FMC Corporation, a pyrethroid manufacturer and member of the Pyrethroid Working Group during the conduct of the study. Larry Sheets is employed by Bayer CropScience, a company that manufactures and sells some of the pyrethroids that were evaluated in this study. Dana Sargent is employed by Bayer CropScience, a company that is a pyrethroid manufacturer and member of the Pyrethroid Working Group. John Clark received funding for research from the Pyrethroid Working Group and carried out at the University of Massachusetts, Amherst.

Keywords

Calcium ion
Chloride ion channels
Clustering
Common mechanism
FOB
Factor analysis
Principal components
Pyrethroid
Sodium ion
Type I
Type II

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10.1016/j.neuro.2009.09.002

Cite this

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title = "Evidence for a separate mechanism of toxicity for the Type I and the Type II pyrethroid insecticides",

abstract = "Neurotoxicity and mechanistic data were collected for six α-cyano pyrethroids (β-cyfluthrin, cypermethrin, deltamethrin, esfenvalerate, fenpropathrin and λ-cyhalothrin) and up to six non-cyano containing pyrethroids (bifenthrin, S-bioallethrin [or allethrin], permethrin, pyrethrins, resmethrin [or its cis-isomer, cismethrin] and tefluthrin under standard conditions. Factor analysis and multivariate dissimilarity analysis were employed to evaluate four independent data sets comprised of (1) fifty-six behavioral and physiological parameters from an acute neurotoxicity functional observatory battery (FOB), (2) eight electrophysiological parameters from voltage clamp experiments conducted on the Nav1.8 sodium channel expressed in Xenopus oocytes, (3) indices of efficacy, potency and binding calculated for calcium ion influx across neuronal membranes, membrane depolarization and glutamate released from rat brain synaptosomes and (4) changes in chloride channel open state probability using a patch voltage clamp technique for membranes isolated from mouse neuroblastoma cells. The pyrethroids segregated into Type I (T-syndrome-tremors) and Type II (CS syndrome-choreoathetosis with salivation) groups based on FOB data. Of the α-cyano pyrethroids, deltamethrin, λ-cyhalothrin, cyfluthrin and cypermethrin arrayed themselves strongly in a dose-dependent manner along two factors that characterize the CS syndrome. Esfenvalerate and fenpropathrin displayed weaker response profiles compared to the non-cyano pyrethroids. Visual clustering on multidimensional scaling (MDS) maps based upon sodium ion channel and calcium influx and glutamate release dissimilarities gave similar groupings. The non-cyano containing pyrethroids were arrayed in a dose-dependent manner along two different factors that characterize the T-syndrome. Bifenthrin was an outlier when MDS maps of the non-cyano pyrethroids were based on sodium ion channel characteristics and permethrin was an outlier when the MDS maps were based on calcium influx/glutamate release potency. Four of six α-cyano pyrethroids (λ-cyfluthrin, cypermethrin, deltamethrin and fenpropathrin) reduced open chloride channel probability. The R-isomers of λ-l-cyhalothrin reduced open channel probability whereas the S-isomers, antagonized the action of the R-isomers. None of the non-cyano pyrethroids reduced open channel probability, except bioallethrin, which gave a weak response. Overall, based upon neurotoxicity data and the effect of pyrethroids on sodium, calcium and chloride ion channels, it is proposed that bioallethrin, cismethrin, tefluthrin, bifenthrin and permethrin belong to one common mechanism group and deltamethrin, λ-cyhalothrin, cyfluthrin and cypermethrin belong to a second. Fenpropathrin and esfenvalerate occupy an intermediate position between these two groups.",

keywords = "Calcium ion, Chloride ion channels, Clustering, Common mechanism, FOB, Factor analysis, Principal components, Pyrethroid, Sodium ion, Type I, Type II",

author = "Breckenridge, \{Charles B.\} and Larry Holden and Nicholas Sturgess and Myra Weiner and Larry Sheets and Dana Sargent and Soderlund, \{David M.\} and Choi, \{Jin Sung\} and Steve Symington and Clark, \{J. Marshall\} and Steve Burr and David Ray",

note = "Funding Information: This research was sponsored by the Pyrethroid Working Group, a trade association of manufacturers of commercial pyrethroid pesticides registered in the United States. Member companies include Amvac, BayerCropScience, Cheminova, Dupont, FMC Corporation, Syngenta, Valent USA Corporation. This work was presented in part at the 2006 Society of Toxicology meeting: Breckenridge C., Holden L., Sheets L., Creek M., Mullen L., Sargent D., Sharp J., Weiner M.L. Principal components and factor analysis of the functional observational battery of 12 pyrethroids. The Toxicologist 2006;90(10):50. Funding Information: Charles Breckenridge is employed by Syngenta, a basic manufacturer of λ-cyhalothrin, cypermethrin, permethrin, tefluthrin. These chemicals were evaluated in this study. All work on this paper by Sielken and Associates with the Pyrethroid Working Group, Wilmington, DE, USA. Myra Weiner is a former employee of FMC Corporation, a pyrethroid manufacturer and member of the Pyrethroid Working Group during the conduct of the study. Larry Sheets is employed by Bayer CropScience, a company that manufactures and sells some of the pyrethroids that were evaluated in this study. Dana Sargent is employed by Bayer CropScience, a company that is a pyrethroid manufacturer and member of the Pyrethroid Working Group. John Clark received funding for research from the Pyrethroid Working Group and carried out at the University of Massachusetts, Amherst. ",

year = "2009",

month = nov,

doi = "10.1016/j.neuro.2009.09.002",

language = "English",

volume = "30",

pages = "S17--S31",

journal = "NeuroToxicology",

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T1 - Evidence for a separate mechanism of toxicity for the Type I and the Type II pyrethroid insecticides

AU - Breckenridge, Charles B.

AU - Holden, Larry

AU - Sturgess, Nicholas

AU - Weiner, Myra

AU - Sheets, Larry

AU - Sargent, Dana

AU - Soderlund, David M.

AU - Choi, Jin Sung

AU - Symington, Steve

AU - Clark, J. Marshall

AU - Burr, Steve

AU - Ray, David

N1 - Funding Information: This research was sponsored by the Pyrethroid Working Group, a trade association of manufacturers of commercial pyrethroid pesticides registered in the United States. Member companies include Amvac, BayerCropScience, Cheminova, Dupont, FMC Corporation, Syngenta, Valent USA Corporation. This work was presented in part at the 2006 Society of Toxicology meeting: Breckenridge C., Holden L., Sheets L., Creek M., Mullen L., Sargent D., Sharp J., Weiner M.L. Principal components and factor analysis of the functional observational battery of 12 pyrethroids. The Toxicologist 2006;90(10):50. Funding Information: Charles Breckenridge is employed by Syngenta, a basic manufacturer of λ-cyhalothrin, cypermethrin, permethrin, tefluthrin. These chemicals were evaluated in this study. All work on this paper by Sielken and Associates with the Pyrethroid Working Group, Wilmington, DE, USA. Myra Weiner is a former employee of FMC Corporation, a pyrethroid manufacturer and member of the Pyrethroid Working Group during the conduct of the study. Larry Sheets is employed by Bayer CropScience, a company that manufactures and sells some of the pyrethroids that were evaluated in this study. Dana Sargent is employed by Bayer CropScience, a company that is a pyrethroid manufacturer and member of the Pyrethroid Working Group. John Clark received funding for research from the Pyrethroid Working Group and carried out at the University of Massachusetts, Amherst.

PY - 2009/11

Y1 - 2009/11

N2 - Neurotoxicity and mechanistic data were collected for six α-cyano pyrethroids (β-cyfluthrin, cypermethrin, deltamethrin, esfenvalerate, fenpropathrin and λ-cyhalothrin) and up to six non-cyano containing pyrethroids (bifenthrin, S-bioallethrin [or allethrin], permethrin, pyrethrins, resmethrin [or its cis-isomer, cismethrin] and tefluthrin under standard conditions. Factor analysis and multivariate dissimilarity analysis were employed to evaluate four independent data sets comprised of (1) fifty-six behavioral and physiological parameters from an acute neurotoxicity functional observatory battery (FOB), (2) eight electrophysiological parameters from voltage clamp experiments conducted on the Nav1.8 sodium channel expressed in Xenopus oocytes, (3) indices of efficacy, potency and binding calculated for calcium ion influx across neuronal membranes, membrane depolarization and glutamate released from rat brain synaptosomes and (4) changes in chloride channel open state probability using a patch voltage clamp technique for membranes isolated from mouse neuroblastoma cells. The pyrethroids segregated into Type I (T-syndrome-tremors) and Type II (CS syndrome-choreoathetosis with salivation) groups based on FOB data. Of the α-cyano pyrethroids, deltamethrin, λ-cyhalothrin, cyfluthrin and cypermethrin arrayed themselves strongly in a dose-dependent manner along two factors that characterize the CS syndrome. Esfenvalerate and fenpropathrin displayed weaker response profiles compared to the non-cyano pyrethroids. Visual clustering on multidimensional scaling (MDS) maps based upon sodium ion channel and calcium influx and glutamate release dissimilarities gave similar groupings. The non-cyano containing pyrethroids were arrayed in a dose-dependent manner along two different factors that characterize the T-syndrome. Bifenthrin was an outlier when MDS maps of the non-cyano pyrethroids were based on sodium ion channel characteristics and permethrin was an outlier when the MDS maps were based on calcium influx/glutamate release potency. Four of six α-cyano pyrethroids (λ-cyfluthrin, cypermethrin, deltamethrin and fenpropathrin) reduced open chloride channel probability. The R-isomers of λ-l-cyhalothrin reduced open channel probability whereas the S-isomers, antagonized the action of the R-isomers. None of the non-cyano pyrethroids reduced open channel probability, except bioallethrin, which gave a weak response. Overall, based upon neurotoxicity data and the effect of pyrethroids on sodium, calcium and chloride ion channels, it is proposed that bioallethrin, cismethrin, tefluthrin, bifenthrin and permethrin belong to one common mechanism group and deltamethrin, λ-cyhalothrin, cyfluthrin and cypermethrin belong to a second. Fenpropathrin and esfenvalerate occupy an intermediate position between these two groups.

AB - Neurotoxicity and mechanistic data were collected for six α-cyano pyrethroids (β-cyfluthrin, cypermethrin, deltamethrin, esfenvalerate, fenpropathrin and λ-cyhalothrin) and up to six non-cyano containing pyrethroids (bifenthrin, S-bioallethrin [or allethrin], permethrin, pyrethrins, resmethrin [or its cis-isomer, cismethrin] and tefluthrin under standard conditions. Factor analysis and multivariate dissimilarity analysis were employed to evaluate four independent data sets comprised of (1) fifty-six behavioral and physiological parameters from an acute neurotoxicity functional observatory battery (FOB), (2) eight electrophysiological parameters from voltage clamp experiments conducted on the Nav1.8 sodium channel expressed in Xenopus oocytes, (3) indices of efficacy, potency and binding calculated for calcium ion influx across neuronal membranes, membrane depolarization and glutamate released from rat brain synaptosomes and (4) changes in chloride channel open state probability using a patch voltage clamp technique for membranes isolated from mouse neuroblastoma cells. The pyrethroids segregated into Type I (T-syndrome-tremors) and Type II (CS syndrome-choreoathetosis with salivation) groups based on FOB data. Of the α-cyano pyrethroids, deltamethrin, λ-cyhalothrin, cyfluthrin and cypermethrin arrayed themselves strongly in a dose-dependent manner along two factors that characterize the CS syndrome. Esfenvalerate and fenpropathrin displayed weaker response profiles compared to the non-cyano pyrethroids. Visual clustering on multidimensional scaling (MDS) maps based upon sodium ion channel and calcium influx and glutamate release dissimilarities gave similar groupings. The non-cyano containing pyrethroids were arrayed in a dose-dependent manner along two different factors that characterize the T-syndrome. Bifenthrin was an outlier when MDS maps of the non-cyano pyrethroids were based on sodium ion channel characteristics and permethrin was an outlier when the MDS maps were based on calcium influx/glutamate release potency. Four of six α-cyano pyrethroids (λ-cyfluthrin, cypermethrin, deltamethrin and fenpropathrin) reduced open chloride channel probability. The R-isomers of λ-l-cyhalothrin reduced open channel probability whereas the S-isomers, antagonized the action of the R-isomers. None of the non-cyano pyrethroids reduced open channel probability, except bioallethrin, which gave a weak response. Overall, based upon neurotoxicity data and the effect of pyrethroids on sodium, calcium and chloride ion channels, it is proposed that bioallethrin, cismethrin, tefluthrin, bifenthrin and permethrin belong to one common mechanism group and deltamethrin, λ-cyhalothrin, cyfluthrin and cypermethrin belong to a second. Fenpropathrin and esfenvalerate occupy an intermediate position between these two groups.

KW - Calcium ion

KW - Chloride ion channels

KW - Clustering

KW - Common mechanism

KW - FOB

KW - Factor analysis

KW - Principal components

KW - Pyrethroid

KW - Sodium ion

KW - Type I

KW - Type II

UR - https://www.scopus.com/pages/publications/71749085258

U2 - 10.1016/j.neuro.2009.09.002

DO - 10.1016/j.neuro.2009.09.002

M3 - Article

C2 - 19766671

AN - SCOPUS:71749085258

SN - 0161-813X

VL - 30

SP - S17-S31

JO - NeuroToxicology

JF - NeuroToxicology

IS - SUPPL.

ER -

Evidence for a separate mechanism of toxicity for the Type I and the Type II pyrethroid insecticides

Abstract

Bibliographical note

Keywords

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