Introduction to Pesticide Biotransformation and Disposition - Pesticide Biotransformation and Disposition - page 2

Exposure and absorption at portals of entry

Distribution to organs and tissues

Excretion

Metabolism to more
toxic metabolites

Metabolism to less
toxic metabolites

Metabolism to
conjugation products

Redistribution to organs and tissues

Interaction with macromolecules
(Protein, DNA, RNA, Receptors, etc.)

Turnover and repair

Toxic effects
Genetic, Carcinogenic, Reproductive, Neurotoxic, etc.

Figure 1.1 Chemical toxicity: a cascade of events.

all chemical reactions of normal body constituents. However, the two terms can usually
be used as synonyms without confusion.

RELEVANCE OF BIOTRANSFORMATION AND DISPOSITION STUDIES

Studies of pesticide disposition, particularly biotransformation, are critical to the
understanding of the toxic mode of action in both target and nontarget organisms.
Biotransformation may result in the formation of less toxic (detoxication) and/or more
toxic (activation) products, while the various other processes shown in Figure 1.1 may
determine the balance between toxic and nontoxic events. While disposition in non-
target species, including humans, is the primary focus of this volume, studies in target
species facilitate the development of more effective, safer pesticides.
Most important, disposition studies facilitate risk analysis. They make possible phy-
siologically based pharmacokinetic studies, since not only is knowledge of the uptake,
distribution, and rate of excretion of the parent chemical necessary, but also that of
the distribution and excretion of its metabolites. Mechanism of action at the molecu-
lar level cannot be defined unless all active metabolites have been identified and their
interactions at the site of action determined. Quantitative structure activity relationship
studies, important for the prediction of both effectiveness and toxicity, likewise depend
on detailed knowledge of metabolites and their formation.