Dealing with Complex Pollution Problems - Organic Pollutants: An Ecotoxicological Perspective - page 246

measure the percent of vitamin K binding sites occupied by rodenticides.
However, the technology is not currently available to do that. On the other
hand, the measurement of increases in plasma levels of undercarboxylated
clotting proteins some time after exposure to rodenticide provides a good
biomarker for this toxic mechanism.
3. Some hydroxy metabolites of coplanar PCBs, such as 4-OH and 3,3′4,5′-tet-
rachlorobiphenyl, act as antagonists of thyroxin (Chapter 6, Section 6.2.4).
They have high affinity for the thyroxin-binding site on transthyretin (TTR) in
plasma. Toxic effects include vitamin A deficiency. Biomarker assays for this
toxic mechanism include percentage of thyroxin-binding sites to which roden-
ticide is bound, plasma levels of thyroxin, and plasma levels of vitamin A.
4. Coplanar PCBs, PCDDs, and PCDFs express ah-receptor-mediated tox-
icity (Chapter 6, Section 6.2.4). Binding to the receptor leads to induction
of cytochrome P450 I and a number of associated toxic effects. Again, toxic
effects are related to the extent of binding to this receptor and appear to
be additive, even with complex mixtures of planar polychlorinated com-
pounds. Induction of P4501A1/2 has been widely used as the basis of a
biomarker assay. Residue data can be used to estimate TEQs for dioxin (see
Chapter 7, Section 7.2.4).
In addition to the foregoing, three further examples in this list (numbers
5-7) deserve consideration. These are (5) interaction of endocrine disrup-
tors with the estrogen receptor, (6) the action of uncouplers of oxidative
phosphorylation, and (7) mechanisms of oxidative stress. Until now only
the first is well represented by biomarker assays that have been employed
in ecotoxicology.
5. Interaction with the estrogen receptor (eR) h a s b e e in i m p o r t a nt i in t h e d evel-
opment of biomarker assays for endocrine disrupting chemicals (EDCs), and
will be discussed in Chapter 15. The considerable range of biomarker assays
(including bioassays) already developed is reviewed by Janssen, Faber, and
Bosveld (1998). A surprisingly diverse range of chemicals can act as agonists
or antagonists for the estrogen receptor, producing “feminizing” or “mas-
culinizing” effects. These include o,p ′-DDE, certain PAHs, PCBs, PCDDS,
PCDFs, alkylphenols, and naturally occurring phyto- and myco-estrogens.
However, it should be borne in mind that some EDCs (e.g., o,p ′-DDE, PCBs)
probably act through their hydroxymetabolites, which bear a closer resem-
blance to natural estrogens than the parent compounds and, second, that oth-
ers (e.g., alkylphenols) are only very weak estrogens.
A number of biomarker assays have been developed for fish. Apart from
a variety of nonspecific endpoints such as organ weight and histochemical
change, vitellogenin synthesis has provided a specific and sensitive endpoint,
which has been very useful for detecting the presence of environmental
estrogens at low concentrations. A number of different cell lines have been
developed for use in bioassays for rapid screening of environmental sam-
ples. These include fish and bird hepatocytes, mouse hepatocytes, human
mammary tumor cells, and yeast cells (Janssen, Faber, and Bosveld 1998).
The endpoints include vitellogenin production, competitive binding to ER,