For purposes of this presentation, toxicokinetics data include those on the chemical’s metabolism, biotransformation, and pharmacokinetics (PK), in that these kinetics data are prepared and analyzed for revealing the detoxification and bioactivation of the chemical and its metabolites in the body.

As mentioned in Slide 10, the U.S. Food Quality Protection Act (FQPA) mandates that EPA and FDA consider aggregate and cumulative exposures in their health risk assessment. Cumulative risk or exposure assessment is that process in which an accumulation is made on exposures to multiple chemicals that cause the same toxic effects by a common mechanism. The common toxic effects caused by these multiple chemicals are likely investigated in different species or not following the same dosing regime. In that case, the doses used in animal studies should be extrapolated to human doses through PB-PK modeling. This approach for dose extrapolation between species or routes of exposure is not feasible, however, unless extensive comparative metabolism and PK data are available.

Toxicokinetics data are also crucial in understanding the extent of biologic interactions by which chemicals exert their toxic effects on living organisms. Without this type of information, the strength-of-evidence and the weight-of-evidence analyses cannot be performed in hazard identification or dose-response assessment. As pointed out by Scala (1991), an understanding of how a toxic agent functions “will help to determine whether the health of the public requires excessively conservative risk models or not.”