Overview of the metabolism and interactions of pesticides in hepatic in vitro systems

Abstract

Public concern about the impact of xenobiotics, including pesticides, on human health is greater than ever before. Pesticides constitute a potential risk to humans who are exposed to them directly and indirectly. Accordingly, the health risk assessment of pesticides is of utmost importance for the protection of human health. Risk assessment needs reliable scientific information, and one source of information is the characterisation of metabolic factors and toxicokinetics. Indeed, quantitative toxicokinetic data in humans are needed for human risk assessment to make reliable comparisons between individuals or between species. Because humans cannot be used as study subjects except in occasional circumstances, we have to rely upon in vitro experiments, human-derived techniques and in vitro–in vivo predictions. These methods combined with the advantage of novel analytical techniques (LC/TOF-MS; LC/MS-MS and LC-NMR) for metabolite identification and quantification enable the development of quantitative chemical-specific assessment factors. Here, we will briefly describe the in vitro techniques used to study in vitro metabolism and interactions, summarise the metabolic and kinetic properties of diuron as an herbicide and demonstrate how to apply current techniques to obtain relevant data for risk assessment.

Keywords:

• pesticides
• metabolism and interactions
• P450
• human-derived in vitro techniques
• risk assessment
• LC-MS

Acknowledgements

This work was funded by a Ministry of Education-supported position from the Finnish Graduate School in Toxicology (ToxGS), by a DRUG2000 grant from the Finnish Funding Agency for Technology (TEKES) and supported by a grant from the Oulu University Scholarship Foundation.