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Critical Consideration of the Multiplicity of Experimental and Organismic Determinants of Pyrethroid Neurotoxicity: A Proof of Concept
Citation:
Wolansky, M. AND R. Tornero-Velez. Critical Consideration of the Multiplicity of Experimental and Organismic Determinants of Pyrethroid Neurotoxicity: A Proof of Concept. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. Taylor & Francis, Inc., Philadelphia, PA, 16(8):453-490, (2013).
Impact/Purpose:
The National Exposure Research Laboratory′s (NERL′s) Human Exposure and Atmospheric Sciences Division (HEASD) conducts research in support of EPA′s mission to protect human health and the environment. HEASD′s research program supports Goal 1 (Clean Air) and Goal 4 (Healthy People) of EPA′s strategic plan. More specifically, our division conducts research to characterize the movement of pollutants from the source to contact with humans. Our multidisciplinary research program produces Methods, Measurements, and Models to identify relationships between and characterize processes that link source emissions, environmental concentrations, human exposures, and target-tissue dose. The impact of these tools is improved regulatory programs and policies for EPA.
Description:
Pyrethroids (PYR) are pesticides with high insecticidal activity that may disrupt neuronal excitability in target and nontarget species. The accumulated evidence consistently showed that this neurophysiologic action is followed by alterations in motor, sensorimotor, neuromuscular, and thermoregulatory responses. Nevertheless, there are some equivocal results regarding the potency of PYR in lab animals. The estimation of potency is an important step in pesticide chemical risk assessment. In order to identify the variables influencing neurobehavioral findings across PYR studies, evidence on experimental and organismic determinants of acute PYR-induced neurotoxicity was reviewed in rodents. A comprehensive analysis of these studies was conducted focusing on test material and dosing conditions, testing conditions, animal models, and other determinants such as testing room temperature. Variations in the severity of the neurotoxicity, under lab-controlled conditions, was explained based upon factors including influence of animal species and age, test material features such as chemical structure and stereochemistry, and dosing conditions such as vehicle, route of exposure, and dose volume. If not controlled, the interplay of these factors may lead to large variance in potency estimation. This review examined the scope of acute toxicological data required to determine the safety of pesticide products, and factors and covariates that need to be controlled in order to ensure that predictivity and precaution are balanced in a risk assessment process within a reasonable time-frame, using acute PYR-induced neurotoxicity in rodents as an exemplar.
URLs/Downloads:
FINAL FINAL ATTACHMENTS LEGENDS - FIG AND TABLES.PDF (PDF, NA pp, 1710.343 KB, about PDF)FINAL FINAL JTEH-R375_SEPT_5_2013_CLEAN.PDF (PDF, NA pp, 288.067 KB, about PDF)
Taylor and Francis
