Factors Determining the Toxicity of Organic Pollutants to Animals and Plants - Organic Pollutants: An Ecotoxicological Perspective - page 59

the sulfhydryl groups of proteins. It should be added that the reactive PAH
epoxides and most of the reactive oxons of OPs are not the original pol-
lutants absorbed by animals; they are unstable metabolites generated by
monooxygenase attack (see Section 2.3.2.2).
2. The pollutant binds to the target without forming a covalent bond. Such
interactions are usually reversible, and examples include the binding of the
stable organochlorine insecticides p,p ′-DDT and dieldrin to Na + channels
and GABA receptors, respectively; the binding of planar PCBs and dioxins
to the Ah receptor the binding of 4 OH`-, 3,3′,4,5′-tetrachlorobiphenyl to the
thyroxine-binding site of transthyretin; and the binding of ergosterol bio-
synthesis inhibitor (EBI) fungicides to a fungal form of cytochrome P450.
The reduction of DDT toxicity to insects with increasing temperature has
been attributed to desorption of DDT from the sodium channel. (The same
phenomenon has been reported with pyrethroid insecticides, which also
interact with the Na + channel.)
The interaction of toxic molecules with their sites of action leads to physiological
effects at the cellular and whole-organism level. The nature of these effects, and their
significance in ecotoxicology, depend upon the site of action. It is noteworthy that the
four most important groups of insecticides are all neurotoxins, albeit working through
different modes of action (Table 2.5). Disturbances of the nervous system can have
far-reaching consequences, especially when they arise in the central nervous system
(e.g., the effects of dieldrin and HCH on GABA receptors of vertebrates). At an early
stage of intoxication, there can be behavioral effects (evidence of behavioral effects
will be discussed in Chapter 16). In another example, the action of endocrine disrup-
tors may lead to deleterious effects on reproduction, as in the case of imposex caused
by TBT in the dog whelk. Also, the reproduction of some raptors can be adversely
affected by eggshell thinning caused by p,p ′-DDE, apparently due to inhibition of
Ca 2+ ATPase. In a further example, anticoagulant rodenticides such as warfarin, brod-
ifacoum, and flocoumafen act as antagonists of vitamin K, which has a critical role
in the synthesis of clotting proteins in the liver of vertebrates. Following exposure to
these compounds, synthesis of clotting proteins in the liver is incomplete, and pre-
cursors of them are released into blood. After a period of days, the level of clotting
proteins falls in the blood, and hemorrhaging occurs. Thus, different modes of action
lead to different toxic effects with differing ecotoxicological consequences.
Mechanism of action can be an important factor determining selectivity. In the
extreme case, one group of organisms has a site of action that is not present in another
group. Thus, most of the insecticides that are neurotoxic have very little phytotoxicity;
indeed, some of them (e.g., the OPs dimethoate, disyston, and demeton- S -methyl) are
good systemic insecticides. Most herbicides that act upon photosynthesis (e.g., triaz-
ines and substituted ureas) have very low toxicity to animals (Table 2.7). The resis-
tance of certain strains of insects to insecticides is due to their possessing a mutant
form of the site of action, which is insensitive to the pesticide. Examples include cer-
tain strains of housefly with knockdown resistance (mutant form of Na + channel that
is insensitive to DDT and pyrethroids) and strains of several species of insects that
are resistant to OPs because they have mutant forms of acetylcholinesterase. These