Neurotoxicity and mechanistic data were collected for six alpha-cyano pyrethroids
(beta-cyfluthrin, cypermethrin, deltamethrin, esfenvalerate, fenpropathrin and lambda-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(v)1.8 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 alpha-cyano pyrethroids, deltamethrin, lambda-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 alpha-cyano pyrethroids (lambda-cyfluthrin, cypermethrin, deltamethrin
and fenpropathrin) reduced open chloride channel probability. The R-isomers of lambda-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, lambda-cyhalothrin, cyfluthrin and
cypermethrin belong to a second. Fenpropathrin and esfenvalerate occupy an intermediate
position between these two groups.