1) If a medicinal product is part of normal food intake, such as a component of a parenteral nutrition preparation (ie. Sodium glycerophosphate, D-glucose monohydrate etc...). How do I make the PDE calculation? what should the PoD be?

2) When the therapeutic effect of a medicinal product is the "critical effect", as it coul be for anthyarithmic agent, EMA states that " A NOAEL based on clinical pharmacodynamic effects should correspond to the highest dose tested which is considered therapeutically inefficacious". What if this data is not available? could I use the lower daily dose as a LOEL?

Or even if it was... what would F3 and F4 be?

F1= 1

F2=10

F3=?

F4=?

F5=1

Thank you