CELL-CULTURE MODELS OF INTERSPECIES SELECTIVITY TO ORGANOPHOSPHORUS INSECTICIDES

In toxicology, the need to reduce uncertainties in human risk assessme nt is met by understanding why species and individuals within that spe cies respond differently to chemical exposure. This kind of informatio n is needed when extrapolating data from experimental (i.e., whole ani mal) systems to the human condition in terms of risk assessment. In 19 93 the Neurotoxicology Division of the Environmental Protection Agency funded several investigators to examine this phenomenon (i.e., inters pecies selectivity) using cell culture models. Organophosphorus (OF) i nsecticides 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 give n, current explanations for it were discussed and contemporary in vitr o models being used to explain it, were described. Data from these stu dies have helped to redefine the underlying mechanisms that characteri ze and influence the cross-species response to insecticides. These exp eriments have refocused the explanation of this phenomenon to include cellular metabolism, target enzyme baseline activities, and receptor-m ediated electrophysiological and second-messenger events. Several inve stigators on this panel also reported on the use of subcellular marker s (e.g., target esterases, second messengers, ionic fluxes) to differe ntiate neuropathy-causing OP compounds from acetylcholinesterase inhib itors. After these presentations, technical considerations used in the design of in vitro neurotoxicity studies were discussed. (C) 1997 Int ox Press, Inc.