title: The effects of combined exposure to the pyrethroids deltamethrin and S-bioallethrin on hippocampal inhibition and skeletal muscle hyperexcitability in rats.
abstract: The default assumption that different pyrethroid insecticides, sharing a common mode of action, will show additivity of toxicity has not always been supported by in vitro measures, some of which have indicated antagonism. Our intention was to see whether the antagonism between pyrethroids of different classes seen in vitro could be reproduced in vivo. We therefore investigated the effects of single and combined exposures to two commonly used pyrethroids, deltamethrin (type II) and S-bioallethrin (type I) given intravenously to anaesthetised rats. We used two quantitative measures that are responsive to pyrethroids: the duration of prolongation of hippocampal dentate granule cell inhibition and the amplitude of the abnormal electromyogram discharge. At equi-toxic doses, S-bioallethrin extended the inter-stimulus interval evoking 50% inhibition in the hippocampus by 30+/-2.2 ms, and deltamethrin extended it by 199+/-21 ms. Combined administration of the same doses of deltamethrin and S-bioallethrin extended hippocampal inhibition by 164+/-14 ms, which did not differ significantly from the effect of deltamethrin alone. S-bioallethrin was without any effect on the electromyogram, and produced no significant change in the amplitude of the abnormal muscle discharges evoked by deltamethrin. The increase in arterial blood pressure evoked by the combination was significantly less than that evoked by either pyrethroid alone (p<0.001). In summary, although our electrophysiological indices provide no support for functional antagonism between these two pyrethroids, they also fail to indicate any summation of effect.
authors.affiliation: MRC Applied Neuroscience Group, School of Biomedical Sciences, University of Nottingham Medical School, Queens Medical Centre, Nottingham, NG7 2UH, United Kingdom. david.ray@nottingham.ac.uk
authors.forename: David E
authors.initials: DE
authors.lastname: Ray
authors.forename: Steven A
authors.initials: SA
authors.lastname: Burr
authors.forename: Timothy
authors.initials: T
authors.lastname: Lister
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000487:Allethrins / Q000633:toxicity*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D007275:Injections, Intravenous; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D009433:Neural Inhibition / Q000187:drug effects*; D009570:Nitriles / Q000633:toxicity*; D011722:Pyrethrins / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012021:Reflex, Abnormal / Q000187:drug effects; D013979:Tibial Nerve / Q000187:drug effects / Q000503:physiopathology; D014202:Tremor / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D000487:Allethrins; D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; C017180:decamethrin; C018465:bioallethrin