Impairments of Endocrine Functions: Causes and Consequences - Ecological Biomarkers: Indicators of Ecotoxicological Effects - page 192

or homeostasis, reproduction, development, and/or behavior.” Consistent with this defi-
nition, the agency has also stated that it “…does not consider endocrine disruption to be
an adverse effect per se , but rather to be a mode or mechanism of action potentially lead-
ing to other outcomes, for example carcinogenic, reproductive, or developmental effects,
routinely considered in reaching regulatory decisions. Evidence of endocrine disruption
alone can influence priority setting for further testing and the assessment of the results of
this testing could lead to regulatory action if adverse effect are shown to occur.”
Classically, potential endocrine disrupters are classified into four categories: natural
hormones, natural chemicals, synthetically produced pharmaceuticals, and man-made
chemicals. The natural hormones from any animal, released into the environment, and
chemicals produced by one species that exert hormonal actions on other animals (e.g.,
human hormones unintentionally reactivated during the processing of human waste in
sewage effluent) may result in changes to aquatic organisms. The natural chemicals include
plant toxins (the so-called phytoestrogens, such as genistein or coumestrol) and fungal tox-
ins. The synthetically produced pharmaceuticals that are intended to be highly hormon-
ally active (contraceptive pills and treatments for hormone-responsive cancers) may also
be detected in sewage effluent. The man-made chemicals and by-products released into
the environment include some pesticides (e.g., DDT and other chlorinated compounds),
plasticizers (bisphenol A, phthalates), degradation products of some alkylphenols, and a
number of industrial chemicals (e.g., PCBs, dioxin, cadmium).
Priority lists of substances have been published in the United States and Europe. In 2009,
the USEPA has established a list of initial pesticide active ingredients and pesticide inert
ingredients to be screened under the Federal Food, Drug, and Cosmetic Act. Toward the
establishment of a priority list of substances, the EU General Directorate for the Environment
has funded studies on endocrine disruptors, the results of which are compiled in a data-
base (http://ec.europa.eu/environment/endocrine/strategy/substances_en.htm#top). Using
expert advice, chemicals were assigned to one of three categories: (1) the substance has evi-
dence of endocrine disrupting activity in at least one species using intact animals; (2) the
substance has at least some in vitro evidence of biological activity related to endocrine dis-
ruption; (3) the substance has no evidence of endocrine disrupting activity, or no data avail-
able. The methodologies recommended by the Organisation for Economic Co-operation and
Development and USEPA to evaluate the potential of these chemicals to interact with estro-
gen, androgen, and TH systems have been recently reviewed (Borgert et al. 2011; Dang et al.
2011). Borgert et al. (2011) have recommended a sequence for running Endocrine Disruptor
Screening Program/Endocrine Screening Battery assays: (1) screening for estrogen and
androgen activity in vitro and in vivo ; (2) screening in vitro for aromatase and steroidogenesis;
(3) multimodal in vivo mammalian screening; (4) in vivo nonmammalian screening.
8.3 Effects of EDCs on Reproductive System
8.3.1 Estrogenic Activities
Numerous organic compounds released in the aquatic environment as a result of indus-
trial, agricultural, and domestic activities can mimic estrogens and have demonstrated
estrogenic activities both in vitro and in vivo . Among them are substances no longer used
in developed countries (polychlorinated biphenyls, organochlorinated pesticides), but also