Comparison of two in vitro activation systems for protoxicant organophosphorous esterase inhibitors

In order to perform in vitro testing of esterase inhibition caused by organ ophosphorous (OP) protoxicants, simple, reliable methods are needed to conv ert protoxicants to their esterase-inhibiting forms. Incubation of parathio n or chlorpyrifos with 0.05% bromine solution or uninduced rat liver micros omes (RLM) resulted in production of the corresponding oxygen analogs of th ese OP compounds and markedly increased esterase inhibition in SH-SY5Y huma n neuroblastoma cells. Neither activation system affected cell viability or the activity of AChE or NTE in the absence of OP compounds. Although parat hion and chlorpyrifos were activated by RLM, bromine activation required fe wer steps and produced more esterase inhibition for a given concentration o f chlorpyrifos. However, RLM activation of OP protoxicants produced metabol ites other than oxygen analogs and may, therefore, be more relevant as a su rrogate for OP biotransformation in vivo. This methodology makes the use of intact cells for in vitro testing of esterase inhibition caused by protoxi cant organophosphate compounds a viable alternative to in vivo tests.