1. LIMITATIONS OF CYTOTOXICITY assays

2. LIMITATIONS OF CYTOTOXICITY TISSUE & SYSTEMIC RESPONSE
PHARMACOKINETICS
TISSUE & SYSTEMIC RESPONSE
METABOLISM

3. PHARMACOKINETICS Difficult to study pharmacokinetics in vitro.
Significant differences in exposure time and concentration of drug, rate of change of drug concentration, tissue penetration clearance and excretion.

5. METABOLISM After liver metabolism-
Many non-toxic substances become toxic and many are detoxified.
Potential toxin should reach the cell in vitro as in vivo.

6. TISSUE AND SYSTEMIC RESPONSE
In vivo responses of tissues-
Inflammatory response
Pyrexia
Oedema
Swelling
Redness
Rashes
Vascular dilation
Kidney failure
Fibrosis