Keywords used in PCS

Important parameters are:

  • In vitro: IC50, which is half of the maximal inhibitory concentration, a measure of the potency of a substance for acting on a specific biological or biochemical function, e.g. an enzyme, cell, cell receptor or microorganism. Typically, IC50 values are expressed as molar concentrations
  • In vivo:
    • The No-Observed-Adverse-Effect-Level (NOAEL) is the level of exposure of an organism, at which no biologically and statistically significant increase in the frequency or severity of any adverse alteration of morphology, function, capacity, growth, development and/or lifespan of an organism is seen
      In drug development, the NOAEL of a new drug is used after application of safety factors to establish a safe clinical starting dose in humans
    • In contrast, the No-Observed-Effect-Level (NOEL) indicates the exposure level at which no biologically and statistically significant increase in the frequency or severity of any effect is seen. Thus, the NOEL also includes e.g. pharmacological effects intended by the treatment. As such, the NOEL is often lower than the NOAEL but also less important than the NOAEL
    • The Lowest-Observed-Adverse-Effect-Level (LOAEL) is the lowest exposure level causing a biologically and statistically significant increase in the frequency or severity of any adverse effect. In regulatory toxicity testing this parameter has low importance.
    • The Lowest-Observed-Effect-Level (LOEL) is defined correspondingly

Typically, the above values are expressed in toxicology as mg/kg bodyweight. Alternatively, mg/m2 body surface can be used.

The extrapolation of the parameters above to different species, in particular from animals to humans (human equivalent dose), is regulated e.g. by FDA