Chemistry Reference
In-Depth Information
Apart from the wider question of effects on natural environment, selectivity is
a vital consideration in relation to the efficacy of pesticides and the risks that they
pose to workers using them and to farm and domestic animals that may be exposed
to them. In designing new pesticides, manufacturers seek to maximize toxicity to
the target organism, which may be an insect pest, vertebrate pest, weed, or plant
pathogen, while minimizing toxicity toward farm animals, domestic animals, and
beneficial organisms. Beneficial organisms include beneficial insects such as pol-
linators and parasites and predators of pests. Understanding mechanisms of tox-
icity can lead manufacturers toward the design of safer pesticides. Physiological
and biochemical differences between pest species and beneficial organisms can be
exploited in the design of new, safer, and more selective pesticides. Examples of
this will be given in the following text. On the question of efficacy, the develop-
ment of resistance is an inevitable consequence of the heavy and continuous use
of pesticides. Understanding the factors responsible for resistance (e.g., enhanced
detoxication or insensitivity of the site of action in a resistant strain) can point
to ways of overcoming it. For example, alternative pesticides not susceptible to
the resistance mechanism may be used. In general, a better understanding of the
mechanisms responsible for selectivity can facilitate the safer and more effective
use of pesticides.
2.2 factorS tHat determIne toxIcIty and PerSIStence
The fate of a xenobiotic in a living organism, seen from a toxicological point of view,
is summarized in Figure 2.1. This highly simplified diagram draws attention to the
main processes that determine toxicity. Three main categories of site are shown in the
diagram, each representing a different type of interaction with a chemical. These are
1. Sites of action. When a chemical interacts with one or more of these, there
will be a toxic effect on the organism if the concentration exceeds a certain
threshold. The chemical has an effect on the organism.
2. Sites of metabolism. When a chemical reaches one of these, it is metabo-
lized. Usually this means detoxication, but sometimes (most importantly)
the consequence is activation. The organism acts upon the chemical.
3. Sites of storage. When located in one of these, the chemical has no toxic effect,
is not metabolized, and is not available for excretion. However, after release
from storage, it may travel to sites of action and sites of metabolism.
In reality, things are more complex than this. For some chemicals, there may be more
than one type of site in any of these categories. Some chemicals have more than one
site of action. The organophosphorous (OP) insecticide mipafox, for example, can
produce toxic effects by interacting with either acetylcholinesterase or neuropathy
target esterase. Also, many chemicals undergo metabolism by two or more types of
enzyme. Pyrethroid insecticides, for example, are metabolized by both monooxyge-
nases and esterases. Also, lipophilic compounds can be stored in various hydropho-
bic domains within the body, including fat depots and in association with “inert”
proteins (i.e., proteins that do not metabolize them or represent a site of action).
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