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Overview of the procedure used to develop dose–response relationship for cognitive health effect end points. The top row shows a current methodology for determining point-of-departure estimates of acetylcholinesterase (AChE) inhibition using animal exposure models, and the bottom row illustrates the proposed methodology for using internal dose metrics to predict cognitive health end points. PD, pharmacodynamic; PBPK, physiologically based pharmacokinetic; RBC, red blood cells.
