Distribution and Effects of Chemicals in Communities and Ecosystems - Organic Pollutants: An Ecotoxicological Perspective - page 87

the protein and the loss of thyroxine and retinol from the blood. Here, measure-
ment of the reduction of binding of thyroxine to transthyretin provides the basis for
a mechanistic biomarker assay that reports changes at the site of action caused by
these metabolites of PCBs (Brouwer et al. 1990, 1998). p,p ′-DDE causes eggshell
thinning in birds by retarding the uptake of Ca ++ across the wall of the shell gland
(Chapter 5). There is still some uncertainty about the exact mechanism by which
p,p ′-DDE retards the movement of Ca ++ into the shell gland, although both inhibi-
tion of calcium ATPase and changes in prostaglandin levels have been implicated
(Lundholm 1997). Again, the secondary effect—thinning of the eggshell—provides
a good monitor of the toxic process. Finally, imposex is a condition that can be
caused by tributyl tin (Chapter 8). It seems probable that the primary effect is to
inhibit the production of testosterone. This point aside, a convenient biomarker assay
measures the development of a penis by the female dog whelk that, when sufficiently
large, blocks the oviduct and causes infertility. Once again, a biomarker assay pro-
vides a convenient measure of the toxic process.
In all of these examples it should be noted that the toxic process occurs through
different stages over a period of time. In some instances (e.g., delayed neuropathy
caused by some OPs, and hemorrhaging caused by warfarin) there may be a delay
of several weeks between initial exposure and the appearance of overt symptoms of
poisoning, which raises two issues. First, it emphasizes the importance of having
sensitive biomarkers that can provide early measures of intoxication before severe
toxicity occurs. Second, if we are to understand toxicity at a deeper level, the dif-
ferent stages in the process need to be understood and be readily measurable. These
issues will be returned to later in the text, especially in Chapters 15 and 16, when
consideration will be given to the development of new biomarker strategies, incorpo-
rating the omics , which have the potential to address both questions (Box 4.3).
A number of attributes are sought when developing biomarker assays. At a practi-
cal level, assays should be robust, inexpensive, and relatively easy for nonspecialists
to use. Unfortunately, some promising assays are really at the stage of being research
tools, only usable by experts with specialized apparatus. There is a need for user-
friendly kits (such as the diagnostic kits that are widely available to medical laborato-
ries) for use in nonspecialist laboratories with relatively simple apparatus. Specificity
is another desirable characteristic, in the sense of identifying a particular mechanism
of toxicity and, therefore, a particular class of organic pollutant. When dealing with
complex cases of pollution, it is extremely valuable to have biomarker assays that can
provide evidence of causal links between levels of particular pollutants (or classes
of pollutant) detected in the environment and associated harmful biological effects.
Examples of such biomarkers include imposex in dog whelks related to tributyl tin,
brain cholinestease inhibition in vertebrates caused by organophosphorous insecti-
cides, and eggshell thinning of some predatory birds caused by p,p ′-DDE (Table 4.2).
Sensitivity is another desirable characteristic that can facilitate the early detection
of sublethal effects. The detection of later effects seen during the terminal stages of
poisoning is of less value.