Summary, Conclusions, and Future Developments - Pesticide Biotransformation and Disposition - page 206

10

CHAPTER

Summary, Conclusions, and Future
Developments

Ernest Hodgson
North Carolina State University, Raleigh, NC, USA

Outline
Introduction

209

Continuing Need for Pesticide Metabolism Studies 210

New Approaches to Pesticide Metabolism 211

Analytical Chemistry 211

Human Studies 211

Toxicogenomics 211

Metabolomics 211

Bioinformatics 211

Conclusions 212

References 212

INTRODUCTION

There is a large literature on the metabolism of pesticides in both target and surrogate
animal species and a much smaller, but growing, literature on human metabolism of
pesticides. However, given the number of pesticides and the importance of this class
of chemicals, much more work is necessary. At the same time, given the effort, time,
and cost in arriving at a complete understanding of pesticide metabolism it appears
unlikely that all of the needed studies can be accomplished by traditional methods.
Studies of pesticide disposition, particularly biotransformation, are critical to the
understanding of the toxic mode of action in both target and nontarget organisms if
new selective pesticides are to be discovered. The balance between activation to toxic
metabolites and detoxication is crucial to this effort.
Disposition studies are also essential for risk analysis. They make possible physio-logi-
cally based pharmacokinetic (PBPK) studies, required for regulatory and other purposes.
Science-based risk assessment is possible only if the mechanism of action at the molecu-
lar level can be defined, and only if all active metabolites have been identified and their
interactions at the site of action determined. Quantitative structure-activity relationship
(QSAR) studies, important for the prediction of both effectiveness and toxicity, likewise
depend on detailed knowledge of metabolites and their formation.