REVISITING THE IMPACT OF BIOLOGICAL AND EXPERIMENTAL CONDITIONS OF LABORATORY ANIMAL STUDIES ON ESTIMATIONS OF RISK OF NEUROTOXICITY BY EXPOSURE TO PESTICIDES IN HUMANS: THE PYRETHROID CASE

WOLANSKY, M.J.; CROFTON, K.M; ROMERO, D.M; TORNERO-VELEZ, ROGELIO

San Francisco, California

Congreso; 51st Annual Meeting and ToxExpoTM; 2012

Society of Toxiclogy

Pyrethroids are potent insecticides that alter nervous system function in target and non-target species by disrupting neuronal excitability. While the accumulated evidence consistently shows that this neurophysiologic action is followed by alterations in motor, sensorimotor, neuromuscular and thermoregulatory responses, there are some equivocal results regarding the potency of pyrethroids in small rodents. According to current guidelines, the estimation of absolute and relative potencies is a critical step in chemical risk assessment. In order to identify the variables influencing neurobehavioral findings across pyrethroid studies, we have reviewed the evidence on experimental and organismic determinants of pyrethroid neurotoxicity in small rodents. A comprehensive analysis of these studies was conducted focusing on test material and dosing conditions, testing conditions, animal model, and other determinants such as testing room temperature. Variations in the severity of the neurotoxicity under laboratory-controlled conditions was found to be mostly explained by the influence of biological factors such as species and age, test material features such as chemical structure, stereochemistry and vehicle, and dosing conditions such as route of exposure and dose-volume. Theoretically, interplay between all effective factors might result in up to ~1,000-fold (o higher) variation in potency estimates. This critical analysis of the pyrethroid case examines the scope of toxicological data required to assure the safety of pesticide products, and the factors and covariates which must be controlled for in order to ensure that predictive power and precaution are balanced in a risk assessment process within a reasonable time frame.