Cell culture models of interspecies selectivity to organophosphorous insecticides

In toxicology, the need to reduce uncertainties in human risk assessment is met by understanding why species and individuals within that species respond differently to chemical exposure. This kind of information is needed when extrapolating data from experimental (i.e., whole animal) systems to the human condition in terms of risk assessment. In 1993 the Neurotoxicology Division of the Environmental Protection Agency funded several investigators to examine this phenomenon (i.e., interspecies selectivity) using cell culture models. Organophosphorous (OP) insecticides were examined since they are characterized by an extremely divergent interspecies response. In 1995, a symposium entitled Novel Insights into Chemical Neurotoxicity, sponsored by the Society for In Vitro Biology featured this research. In it, a historical overview of the phenomenon of interspecies selectivity to OP insecticides was given, current explanations for it were discussed and contemporary in vitro models being used to explain it, were described. Data from these studies have helped to redefine the underlying mechanisms that characterize and influence the cross-species response to insecticides. These experiments have refocused the explanation of this phenomenon to include cellular metabolism, target enzyme baseline activities, and receptor-mediated electrophysiological and second-messenger events. Several investigators on this panel also reported on the use of subcellular markers (e.g., target esterases, second messengers, ionic fluxes) to differentiate neuropathy-causing OP compounds from acetylcholinesterase inhibitors. After these presentations, technical considerations used in the designed of in vitro neurotoxicity studies were discussed.