Validity and reliability of in vitro systems in safety evaluation.

In vitro data could make an important contribution to the application of the proposed scheme for the subdivision of the usual 10-fold safety factors (used in risk assessment for inter-species and inter-individual differences) into two separate aspects of toxicokinetics and toxicodynamics. Whereas toxicokinetics (or delivery of the chemical to its site of action via the general circulation) is amenable to direct in vivo measurement, toxicodynamics (or the assessment of the sensitivity of the target tissue to the presence of the chemical) is open to in vitro investigation. Human risk assessment requires human data to be able to replace any of the default safety (or uncertainty) factors (Renwick, 1993). Because human tissues are of limited availability, it is likely that the main quantitative contribution of in vitro data will be to allow chemical specific inter-species differences in toxicodynamics to replace the proposed default value. Although in vitro data from human tissues could be used to define human variability in target organ sensitivity (toxicodynamics) this would require a large number of specimens and the variability detected in vitro should be representative of that present in vivo.