Endocrine-Disrupting Chemicals and Their Environmental Impacts - Organic Pollutants: An Ecotoxicological Perspective - page 278

free estrogen in the cell and/or agonistic binding of the compound to an estrogen
receptor (Guillette et al . 2000). In vivo tests in mammals for quantifying the effects
of EDCs include the Hershberger assay, where the principle relies on castration
of male rats to remove the source of endogenous androgens; thus, any androgenic
response is due to the test chemical, the uterotrophic assay, in which uterus growth is
measured as a response to estrogens (Yamasaki et al. 2003; Clode 2006) and various
reproductive performance tests. In fish, in vivo tests for EDCs include short-term
exposures assays that measure VTG induction and effects on the development of
secondary sex features (that are sex hormone dependent), various tests to measure
effects on reproductive performance, and full fish life-cycle tests. In amphibians,
larval development tests are being devised to test for chemicals with thyroid activity
(Gutleb et al. 2007). For invertebrates, in vivo tests for EDCs are generally focused
on development and reproductive endpoints and measured over at least one genera-
tion (Gourmelon and Ahtiainen 2007) . These tests, however, are often not specific
for EDCs and this, together with a general lack of knowledge regarding the hormone
systems of most invertebrates, has in many cases made interpretations on the mecha-
nism of the biological effects difficult.
Advantages of in vivo test systems for EDCs are that they allow for metabolism
and bioconcentration of the compound of interest. The importance of this is illus-
trated by the fact that we now know that there are a variety of EDCs for which it is
their products of metabolism rather than the parent compound that are endocrine-
active (e.g., for the products of metabolism of the pesticides DDT, vinclozolin, and
methoxychlor), and many are lipophilic and bioconcentrate/bioaccumulate. The dis-
advantages of in vivo approaches compared with in silico and in vitro approaches
are associated with their inherent higher costs and the desire to reduce the number of
animals used in chemical testing. Furthermore, endpoints measured in some of the
in vivo tests for EDCs are not necessarily specific for a single mode of action (e.g.,
for reproduction). Thus, ideally included in in vivo tests when assessing for effects of
EDCs on growth, development, and reproduction are biomarkers that inform on the
mode of action. For more detailed assessments on the various assays for testing and
screening EDCs, we would refer the reader to the following articles: Zacharewski
(1997), Gray (1998), O'Connor et al . (2002), and Clode (2006).
What is important to emphasize is that, given the range of known EDCs, their
potential to act with more than one mechanism of action, and ability of some chem-
icals to mediate effects via multiple tissues, no single effective test exists for an
“endocrine disrupter”; rather, a suite of approaches is required to capture the spec-
trum of possible effects.
15.6 a LengtHenIng LISt of edc s
The list of chemicals with endocrine-disrupting activity has increased considerably
with the systematic screening of chemicals employing some of the methods described
in the previous section. Here we expand on the list of known EDCs to illustrate the
diversity of chemicals of concern, but the list is by no means exhaustive.