Summary, Conclusions, and Future Developments - Pesticide Biotransformation and Disposition - page 208

NEW APPROACHES TO PESTICIDE METABOLISM
Analytical Chemistry
The current status of the analytical chemistry techniques used in pesticide metabolism
studies is summarized in Chapter 2. It should be noted that the improvement in these
techniques with regard to both sensitivity and chemical structure characterization has,
in the past few decades, been dramatic and far exceeds our capacity to understand the
significance of the minute quantities of a toxicant that can be detected and character-
ized. It is also true that, without these advances, it would not be possible to realize the
potential of proteomics and metabolomics.
Human Studies
Although metabolic studies on surrogate animals will continue to be necessary, the
current expansion of human studies will continue, particularly since the new paradigm
for risk assessment ( National Research Council, 2007 ) depends heavily on human cell
lines and other human-derived information, thus minimizing the need for extrapola-
tion from surrogate animal to human. These studies have been facilitated by the avail-
ability of human hepatocytes, other human-derived cell lines, human cell fractions
such as microsomes and cytoplasm, and recombinant human XMEs. Although studies
of the effects of polymorphisms on pesticide metabolism are few, new genomic tech-
niques will greatly speed up this approach.
Toxicogenomics
Toxicogenomics describes how chemical stressors such as pesticides affect the entire
genome, combining information from genome-wide mRNA profiling; protein profil-
ing, or proteomics; changes in the metabolome, or metabolomics; genetic susceptibility;
gene-environment interactions; and the computational models necessary to make gen-
eralizations from the data produced and thus relate chemical toxicity to human disease
( Tennant, 2002; Waters and Fostel, 2004; Bogert, 2007 ).
Metabolomics
Metabolomics, as used in toxicogenomics, describes the changes in the metabolome,
the total of all normal metabolites. However, the techniques of metabolomics can be
used in a more restricted sense in pesticide metabolism studies, namely to describe the
total of all metabolites (including all primary and secondary metabolites) of a toxicant
administered to an organism or cell line.
Bioinformatics
Bioinformatics was originally defined as the application of information technol-
ogy to molecular biology. While this is still of critical importance, bioinformatics has