Dealing with Complex Pollution Problems - Organic Pollutants: An Ecotoxicological Perspective - page 245

biomarker responses and are inexpensive, rapid, and simple to use (see Section 13.5).
These can be used alone or in combination with standard toxicity tests, and some of
them identify the mechanisms responsible for toxic effects, thus indicating the types
of compounds involved.
13.3 SHared mecHanISm of actIon—an
Integrated BIomarker aPProacH to
meaSurIng tHe toxIcIty of mIxtureS
A very large number of toxic organic pollutants, both manmade and naturally occur-
ring, exist in the living environment. However, they express their toxicity through a
much smaller number of mechanisms. Some of the more important sites of action of
pollutants were described earlier (Chapter 2, Section 2.3). Thus, a logical approach
to measuring the toxicity of mixtures of pollutants is to use appropriate mechanistic
biomarker assays for monitoring the operation of a limited number of mechanisms of
toxic action and to relate the responses that are measured to the levels of individual
chemicals in the mixtures to which organisms are exposed (Peakall 1992, Peakall
and Shugart 1993). Such an approach can provide an index of additive toxicity of
mixtures, which takes into account any potentiation of toxicity at the toxicokinetic
level (Walker 1998c). Mechanistic biomarkers can be both qualitative and quantita-
tive; they identify a mechanism of toxic action and measure the degree to which it
operates. Thus, they can provide an integrated measure of the overall effect of a
group of compounds that operate through the same mechanism of action. Where the
mechanism of action is specific to a particular class of chemicals, it can be related to
the concentrations of components of a mixture which belong to that class.
Four examples will now be given of such mechanistic biomarker assays that can give
integrative measures of toxic action by pollutants, all of which have been described
earlier in the text. Where the members of a group of pollutants share a common mode
of action and their effects are additive, TEQs can, in principle, be estimated from their
concentrations and then summated to estimate the toxicity of the mixture. In these
examples, toxicity is thought to be simply related to the proportion of the total number
sites of action occupied by the pollutants and the toxic effect additive where two or
more compounds of the same type are attached to the binding site.
1. the inhibition of brain cholinesterase is a biomarker assay for organophos-
phorous (OP) and carbamate insecticides (Chapter 10, Section 10.2.4). OPs
inhibit the enzyme by forming covalent bonds with a serine residue at the
active center. Inhibition is, at best, slowly reversible. The degree of toxic effect
depends upon the extent of cholinesterase inhibition caused by one or more
OP and/or carbamate insecticides. In the case of OPs administered to verte-
brates, a typical scenario is as follows: sublethal symptoms begin to appear at
40-50% inhibition of cholinesterase, lethal toxicity above 70% inhibition.
2. The anticoagulant rodenticides warfarin and superwarfarins are toxic
because they have high affinity for a vitamin K binding site of hepatic
microsomes (Chapter 11, Section 11.2.4). In theory, an ideal biomarker would