From in vitro hepatic metabolic studies towards human health risk assessment: Two case studies of diuron and carbosulfan

• Human data are needed to improve human health risk assessment.
• Difficulties using generalized default assessment factors were explained.
• In vitro human-derived techniques for testing metabolism in vitro were described.
• In vitro characterization of xenobiotic metabolism were discussed.
• Two case studies of herbicide diuron and insecticide carbosulfan were given.

Risk assessment of environmental pollutants is an absolutely essential tool in the overall process of protecting public health. Risk assessment needs reliable scientific information and one source of information is the characterization of metabolic fate and toxicokinetics of environmental pollutants. The aim of in vitro characterization is to produce relevant information on metabolism and interactions to anticipate and ultimately predict what happens in vivo in humans. Because human data is most appropriate to improve human risk assessment, the best option is to rely upon human-derived in vitro models and obtain quantitative toxicokinetics data from in vitro systems for the comparison between species or individuals. In short, based on our studies of pesticide metabolism and interactions, we have used in vitro metabolism data in human and animal hepatic in vitro models and clearance testing data to calculate chemical-specific adjustment factors, instead of fixed uncertainty factors, to be employed as an alternative and more realistic model for human health risk assessment of pesticides and other environmental pollutants.

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