Mechanisms of Chronic OP Toxicity: cholinergic-independent pathway

In rodent models, pre- & peri-natal organophosphate exposures have direct effects on cellular processes unrelated to cholinesterase inhibition.^{30, 31}

• Cholinergic-independent effects occur at lower exposure levels than levels required to affect cholinesterase
• Developing cardiac ³⁴, nervous ³² & muscle ³³ tissues shown to be adversely affected
• These findings may underlie emerging epidemiological evidence associating deficits in memory and learning with in utero or early childhood OP exposure:
  • Traditionally, OP’s thought to only effect cholinergic nerve terminals
  • Acetylcholine is NOT the primary neurotransmitter involved in processes such as memory & learning.
  • The cholinergic-independent OP toxicity observed during rodent development offers a biological explanation that could underlie the association between OP exposures and non-cholinergic neural endpoints in children.