Age-related differences in sensitivity to organophosphorus pesticides

Organophosphorus (OP) pesticides are used extensively throughout the world to control undesirable pest species. The primary mechanism of action for OP insecticides is inhibition of acetylcholinesterase (AChE), an enzyme dynamically involved in cholinergic neurotransmission. Extensive inhibition of AChE leads to accumulation of acetylcholine in the synapse, disruption of normal impulse flow and subsequent signs of toxicity, including autonomic dysfunction, involuntary movements, muscle fasciculations and a host of others. It is generally believed that young individuals are more sensitive to the neurotoxic effects of these agents relative to adults. Essentially all studies addressing age-related differences in sensitivity to these toxicants have examined responses to acute exposures, however, using acute toxicity (lethality) as the endpoint. As the biochemical mechanism of toxicity for this class of toxicants (inhibition of AChE) is well known and considering that low level, repeated exposures are of great concern to the general public, we propose that evidence of neurochemical alterations, especially when exposures occur during development and maturation, is a more relevant endpoint of toxicity than lethality for estimating susceptibility. This report briefly summarizes previous and ongoing work in our laboratory which examines the relative sensitivity to these toxicants between young and adult rats.