Chemistry Reference
In-Depth Information
chemical will be to living organisms. Selectivity is due to the differential opera-
tion of toxicokinetic and toxicodynamic processes between different species, strains,
sexes, or age groups (see Section 2.5). In the study of the basis of selective toxicity
(e.g., resistance of insects to insecticides), it is advantageous to design experiments
that permit the distinction between toxicokinetic and toxicodynamic factors (for fur-
ther discussion, see Walker 1994).
Most of the organic pollutants described in the present text act at relatively low con-
centrations because they, or their active metabolites, have high affinity for their sites of
action. If there is interaction with more than a critical proportion of active sites, distur-
bances will be caused to cellular processes, which will eventually be manifest as overt
toxic symptoms in the animal or plant. Differences between species or strains in the affin-
ity of a toxic molecule for the site of action are a common reason for selective toxicity.
It should also be mentioned that some compounds of relatively low toxicity act as
physical poisons, although such pollutants are seldom important in ecotoxicology. They
have no known specific mode of action, but if they reach relatively high concentrations
in cellular structures, for example, membranes, they can disturb cellular processes.
Examples include certain ethers and esters, and other simple organic compounds.
Tables 2.6 and 2.7 give examples of the modes of action of pollutants in animals
and in plants/fungi, respectively. It is noteworthy that many of the chemicals repre-
sented are pesticides. Pesticides are designed to be toxic to target species. On the other
hand, manufacturers seek to minimize toxicity to humans, beneficial organisms and,
more generally, nontarget species. Selective toxicity is an important issue. Regardful
of the potential risks associated with the release of bioactive compounds into the envi-
ronment, regulatory authorities usually require evidence of the mode of toxic action
before pesticides can be marketed. Other industrial chemicals are not subject to such
strict regulatory requirements, and their mode of action is frequently unknown.
The examples given in Tables 2.6 and 2.7 illustrate the wide range of different mech-
anisms by which pollutants cause toxic effects. The following account will focus on cer-
tain broad issues concerning mode of action. A more detailed description of individual
examples will be given in later chapters devoted to particular types of pollutants.
Many of the pollutants expressing high toxicity to animals are lipophilic in char-
acter. This appears to be a consequence of toxicokinetic factors. After absorption,
lipophilic compounds tend to remain within the organism, and effective excretion
depends on their enzymic conversion to water-soluble and readily excretable prod-
ucts (see Section 2.3.2.1). They tend to associate with membranes and hydrophobic
macromolecules within the body, thus facilitating interaction with enzymes, recep-
tors for chemical messengers, and pore channels. Water-soluble organic compounds,
on the other hand, tend to be rapidly excreted unchanged and do not tend to associate
with lipophilic structures within the organism.
Broadly speaking, toxic interactions between chemicals and cellular sites of
action are of two kinds:
1. The pollutant (xenobiotic) forms a stable covalent bond with its target.
Examples include the phosphorylation of cholinesterases by the oxon forms
of OPs, the formation of DNA adducts by the reactive epoxides of benzo[
a
]
pyrene and other PAHs, and the binding of organomercury compounds to
Search WWH ::
Custom Search