Citation:

Moser, V. C. Evidence for non-acetylcholinesterase mechanisms in pesticide-induced developmental neurotoxicity. Presented at Neurotoxicology Association Meeting, June 09 - 13, 2013.

Impact/Purpose:

This abstract will be presented at the biannual International Neurotoxicology Association meeting June 9-13, 2013, Egmond aan Zee, The Netherlands

Description:

Acetyicholinesterase inhibition is a well-established mode of action for adverse effects of organophosphorus and carbamate pesticides, and the use of this endpoint in regulatory considerations has been assumed to be protective of downstream cholinergic effects. It has been questioned whether neurodevelopmental outcomes are also a consequence of this enzyme inhibition, or whether there are alternative non-cholinesterase mechanisms by which these chemicals alter key events in nervous system development. There is a growing body of literature in laboratory animals indicating that gestational and/or postnatal exposure may cause persistent behavioral effects into adulthood, as well as emerging epidemiological reports of neurodevelopmental outcomes in children. Common experimental findings are alterations in motor activity, cognitive function, and affective and social behaviors in rats or mice, as well as disrupted neuromotor and cognitive development in children. However, the data do not provide evidence for a characteristic pattern of effects. This may suggest nonspecific alterations in neurobehavioral function, but it may also be the result of considerable differences in exposure parameters, experimental designs, test methods and equipment, populations and animal models, and a host of other variables. A number of pesticides have been implicated, but the database for chiorpyrifos is the largest and thus those studies influence any evaluations of trend. Specific attribution of these effects to acetylcholinesterase inhibition has been hampered by insufficient characterization (time-course, dose-response) on this endpoint such that actual levels of inhibition during critical windows of susceptibility are not known. Likewise, cholinesterase data are not available for most epidemiological studies, but measured exposure levels are considered not likely to result in inhibition. A review of these studies suggests a need to explore alternative modes of action in the context of cholinesterase inhibition. This is an abstract of a proposed presentation and does not reflect US EPA policy.

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