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EFFECTS OF PYRETHROIDS ON VOLTAGE-SENSITIVE CALCIUM CHANNELS: A CRITICAL EVALUATION OF STRENGTHS, WEAKNESSES, DATA NEEDS, AND RELATIONSHIP TO ASSESSMENT OF CUMULATIVE NEUROTOXICITY.
Citation:
Shafer, T J. AND D. A. Meyer. EFFECTS OF PYRETHROIDS ON VOLTAGE-SENSITIVE CALCIUM CHANNELS: A CRITICAL EVALUATION OF STRENGTHS, WEAKNESSES, DATA NEEDS, AND RELATIONSHIP TO ASSESSMENT OF CUMULATIVE NEUROTOXICITY. TOXICOLOGY AND APPLIED PHARMACOLOGY 196:303-318, (2004).
Impact/Purpose:
This manuscript will be of interest to individuals in the Office of Pesticides who are involved in making decisions regarding the cumulative risk of pyrethroid compounds, as well as by the general scientific community interested in mechanisms of pyrethroid neurotoxicity.
Description:
A recently published review (Soderlund et al., 2002, Toxicology 171, 3-59.) of the mechanisms of acute neurotoxicity of pyrethroid compounds postulated that voltage-sensitive calcium channels (VSCC) may be a target of some pyrethroid compounds and that effects on VSCC may contribute to the neurotoxicity of pyrethroid compounds. If so, this would influence cumulative risk assessment decisions.
The attached manuscript examines in detail the data for effects of pyrethroids on VSCC and provides a critical assessment of the strenghts and weaknesses of that data. It concludes that based on the present scientific evidence, there is not sufficient data to accept nor reject the hypothesis that effects on VSCC contribute to pyrethroid neurotoxicity.
The attached manuscript also outlines the data needed in order to understand better the potential role of VSCC in pyrethroid neurotoxicity.
The attached manuscript also reviews the roles of VSSC in nervous system function and development, and gives examples of the ramifications of disrupted VSCC function. Furthermore, it briefly discusses subpopulations of humans who may be more susceptible to disruption of VSCC function based on existing disease states involving VSCC.
This manuscript will be of interest to individuals in the Office of Pesticides who are involved in making decisions regarding the cumulative risk of pyrethroid compounds, as well as by the general scientific community interested in mechanisms of pyrethroid neurotoxicity.