(log ppb) HPRT VF (x 10

Metabolism Studies:
Liver in vitro metabolism systems
Model
Isolated perfused liver
Liver slices
Hepatocytes
Liver cell lines
Subcellular fractions
Genetically
engineered cells
Liver in vitro systems: Limitations
Limitations
Fresh tissue needed; short-term viability (2-3h); study of one or a few
compounds only; humans excluded; low reduction of animal numbers
Fresh tissue needed; limited viability (~24h); damaged cells at the
surface; marginal aeration of inner cells; slow transport; bile collection
excluded
Specific techniques and well-established procedures needed; Liver
architecture lost, enzyme levels decrease during culture; batch variability
Poor or absent enzyme expression; limited enzyme activities; genotype
and phenotype instability; not many adequately characterised cell lines
Microsomes contains only CYPs, FMOs and UGTs; co-factors addition is
necessary; extrapolation to in vivo limited; induction effects excluded;
partial metabolic profile; short-term incubation
Limited enzyme number per experiment → pilot study needed; shortterm
study; Extrapolation to the in vivo situation limited
Modified according to Coecke S et al. (2006) ATLA, 34, 49-84; Guillouzo A (1998) Environmental Health Perspectives106(2), 511-532; Plant N (2004) DDT 9(7), 328-
336; Pelkonen O et al. (2004) Basic & Clinical Pharmacology & Toxicology 96, 167-175