Biology Reference
In-Depth Information
1
CHAPTER
Introduction to Pesticide
Biotransformation and Disposition
Ernest Hodgson
North Carolina State University, Raleigh, NC, USA
Outline
Introduction
1
Relevance of Biotransformation and Disposition Studies
2
References
3
INTRODUCTION
It should be emphasized that, although pesticides and their use have many positive
attributes, they are toxicants and, in terms of their interactions with living organisms,
are xenobiotics, and are processed in the same way as other xenobiotics such as clinical
drugs and industrial chemicals.
It should also be emphasized that their toxicity is not due to a single defining
molecular event or interaction, but rather a cascade of events beginning with expo-
sure and culminating with the expression of one or more toxic endpoints. This cascade
(
Figure 1.1
) includes adsorption, distribution, metabolism (both detoxication and acti-
vation), distribution of metabolites, interaction with cellular macromolecules (such as
RNA, DNA, and proteins), repair, and excretion. The processes involved may be revers-
ible to a greater or lesser extent, they may include alternative pathways, and they may
be modified by chemical and physiological interactions. Thus, exposure to a toxicant
does not inevitably lead to a toxic endpoint; metabolism, excretion, or repair may ren-
der the original exposure without effect (
Hodgson, 2010a
). Finally, these processes and
the genes, enzymes, transporters, receptors, etc., involved are all subject to considerable
variation with cell type, organ, individual, species, and strain.
The aspects covered in this volume include adsorption, distribution, biotransformation
(metabolism), and excretion and are collectively known as disposition. Biotransformation
(metabolism), a more specialized term and a subdivision of disposition, of a xenobiotic is
the total of all of the chemical transformations of that xenobiotic taking place in a living
organism. In the case of xenobiotics (including pesticides), the use of the term disposition
is often preferred to metabolism, since the latter is most often used to describe the total of
