Vol. 119, No. 9 News | Science SelectionsOpen AccessTesting the Dose Addition Hypothesis: The Impact of Pyrethroid Insecticide Mixtures on Neuronsis accompanied byAdditivity of Pyrethroid Actions on Sodium Influx in Cerebrocortical Neurons in Primary Culture Kris S. Freeman Kris S. Freeman Search for more papers by this author Published:1 September 2011https://doi.org/10.1289/ehp.119-a399aAboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Pyrethroid insecticides are used extensively in agriculture and in homes to control fleas, cockroaches, bedbugs, and other insects. In a new in vitro study researchers tested the hypothesis that mixtures of pyrethroids have a dose-additive effect—that is, that pyrethroids as a chemical group produce toxicity in mammals via a common mode of action and that the combined toxicity of a pyrethroid mixture reflects the sum of its constituents’ toxicities [EHP 119(9):1239–1246; Cao et al.]. Using increased sodium ion influx as a specific functional measure of toxicity, the researchers found that effects of a mixture of commonly used pyrethroids were consistent with a dose-additive effect on mammalian neurons.Pyrethroids act on the nervous system by disrupting the normal function of voltage-gated sodium channels (VGSCs), which control the influx of sodium ions into neurons to transmit nerve signals. When VGSCs open, the influx of sodium generates the nerve signal; when they close, the electrical signal halts abruptly. Pyrethroids bind to VGSCs and delay their closing, which causes repetitive nerve stimulation that can lead to muscle tremors as well as interfere with the ability of the channels to respond to stimulation.Previous research demonstrated that a mixture of 11 pyrethroids had a dose-additive effect on the rat nervous system, decreasing the animals’ motor activity at doses below the threshold dose of each constituent compound. The authors of the current study exposed neurons cultured from the cerebral cortices of embryonic mice to the same 11 pyrethroids, then examined how VGSCs responded. To measure sodium influx without disrupting cell function, neurons were treated with a sodium-sensitive dye that fluoresced when VGSCs were open.Seven of the pyrethroids tested increased sodium influx in a dose-dependent manner (from highest to lowest potency: deltamethrin, S-bioallethrin, β-cyfluthrin, λ-cyhalothrin, esfenvalerate, telfluthrin, fenpropathrin). Cypermethrin and bifenthrin had only a marginal effect on sodium influx, whereas permethrin and resmethrin had no effect. Despite these variations in activity, the results when neurons were exposed to all 11 compounds together were consistent with a cumulative, dose-additive effect on neuronal sodium influx.People are commonly exposed to low doses of pyrethroid mixtures, which tend to persist as residues on treated surfaces and in household dust. Currently the U.S. Environmental Protection Agency is determining whether a cumulative dose-additive model is appropriate to evaluate potential human health effects of pyrethroid mixtures. This model shows that simultaneous exposure to multiple compounds will produce an effect that is consistent with additivity at the VGSC molecular target.FiguresReferencesRelatedDetailsRelated articlesAdditivity of Pyrethroid Actions on Sodium Influx in Cerebrocortical Neurons in Primary Culture10 June 2011Environmental Health Perspectives Vol. 119, No. 9 September 2011Metrics About Article Metrics Publication History Originally published1 September 2011Published in print1 September 2011 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.