Table 10.

Essential considerations and lessons learnt on the ADME characterization and PBK model development for the 3 UV filters which are highly plasma protein bound

1. Consider real-life use practices and habits in PBK model simulations of UV filters exposure

2. Variability in skin absorption parameters must be accounted for in PBK models

3. Highly lipophilic, protein-bound UV filters are difficult to test due to their nonspecific binding nature in in vitro assays, which could affect data acceptance and interpretation

4. Heat-inactivated controls are appropriate negative controls in hepatocyte stability assays for highly lipophilic, protein-bound chemicals

5. The correction for Fup in traditional well-stirred liver model may not be suitable for calculating liver clearance of highly protein-bound chemicals

6. Accumulation of UV filters occur with successive doses until steady state

7. ADME testing guidelines are needed for challenging chemicals