EPA SAP to discuss integrated strategies to characterize juvenile sensitivity to pyrethroids

The Office of Pesticide Programs (OPP) at EPA has announced a meeting of the FIFRA Scientific Advisory Panel for May 19-21, 2015 to "consider and review research to evaluate the potential for juvenile sensitivity to pyrethroids."  Specifically, OPP is working on a re-evaluation of human health effects of pyrethroids and pyrethrins under registration review and, under direction of an SAP convened in July 2010, the Panel proposed a more modern approach to assessing juvenile and post-natal sensitivity as current methods (i.e. developmental neurotoxicity assays) were inadequate for this endpoint.  This more modern approach embraces the recommendations of the landmark National Academies of Sciences report on Toxicity Testing in the 21st Century by employing a integrated strategy relying on in vitro studies, targeted in vivo studies, and physiologically-based pharmacokinetic (PBPK) models.  

Specifically, the SAP will consider an industry proposal that follows this modern approach. The Council for the Advancement of Pyrethroid Human Health Risk Assessment (CAPHRA) is looking to expand its past work evaluating the "potency of pyrethroids to human sodium channels and transplantation of adult and juvenile rat synaptic membrane into oocytes" done with deltamethrin and permethrin and expand this to be more applicable across pyrethroids and pyrethrins by developing integrates testing plans and collecting targeted data sets amenable to read across and other in silico approaches for the rest of the chemical family.

A solid approach that directs resources where they need to go, saves animal life and based on M³ode of Action.


From the announcement to be published in tomorrow's Federal Register

"Based on feedback from the SAP and the agency, the industry research proposal was revised. Since late 2010, the Council for the Advancement of Pyrethroid Human Health Risk Assessment (CAPHRA) has worked with industry and academic scientists to develop assays and models to assess the potential for juvenile post-natal sensitivity to pyrethroids. The on-going research effort is organized around the adverse outcome pathway (AOP) for pyrethroids: Alterations with voltage-gated sodium channels (VGSC), leading to alterations in membrane excitability and firing potentials and ultimately to in vivo clinical syndromes. Specifically, the CAPHRA is evaluating the potency of pyrethroids to human sodium channels and transplantation of adult and juvenile rat synaptic membrane into oocytes. In addition, the CAPHRA is conducting targeted in vivo studies on behavioral metrics and developing PBPK models. The research, thus far, has focused on development of the overall approach using data for deltamethrin and permethrin (Type II and Type I pyrethroids, respectively). The CAPHRA research is at a point where feedback on extending this research to the other pyrethroids would be constructive. The CAPHRA proposal is to use the knowledge gained with deltamethrin and permethrin to develop more targeted data sets using read across and computational approaches (i.e., less data generation) for other pyrethroids. As such, the agency will be seeking the SAP's advice on the current state of the science with the CAPHRA research effort and proposals for next steps which include extension of data on deltamethrin and permethrin to other pyrethroids."