The last two decades have witnessed growing scientific concerns and public debate over the potential adverse effects that may result from exposure to a group of chemicals that have the potential to alter the normal functioning of the endocrine system in wildlife and humans. Concerns regarding exposure to these EDCs are due primarily to 1) adverse effects observed in certain wildlife, fish, and ecosystems; 2) the increased incidence of certain endocrine-related human diseases; and 3) endocrine disruption resulting from exposure to certain environmental chemicals observed in laboratory experimental animals. These concerns have stimulated many national governments, international organizations, scientific societies, the chemical industry, and public interest groups to establish research programs, organize conferences and workshops, and form expert groups and committees to address and evaluate EDC-related issues. Many of the proceedings of these workshops and/or committees have been published (see Table 2.1) and served as background material for this publication.
However, in the light of continuing uncertainties and highly publicized concerns, the International Programme on Chemical Safety was requested to provide an objective, global assessment of the current state-of-the-science relative to environmental endocrine disruption in humans, experimental studies, and wildlife species. This assessment builds on existing reviews and documents but is not intended to 1) cover all of the endocrine systems that may be disrupted by environmental exposures, 2) assess available test methodologies for detecting EDCs, or 3) address risk assessment and risk management issues. Rather, it focuses on the global peer-reviewed scientific literature where the associations between environmental exposures and adverse outcomes have been demonstrated or hypothesized to occur via mechanisms of endocrine disruption. Endocrine disruption is not considered a toxicological end point per se but a functional change that may lead to adverse effects. For the purposes of this document, a slight modification of the Weybridge (1996) definition was used and endocrine disruptors are defined in a generic sense as follows:
- An endocrine disruptor is an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub)populations.
- A potential endocrine disruptor is an exogenous substance or mixture that possesses properties that might be expected to lead to endocrine disruption in an intact organism, or its progeny, or (sub)populations.
Concerns regarding EDCs have generated a vast number of divergent research studies conducted under various conditions and examining various outcomes. It is extremely rare that a single study could provide all the necessary relevant information to link a particular exposure scenario to a particular health outcome in wildlife or humans. Therefore, it is essential to evaluate the entire body of relevant knowledge. A unique feature of this assessment document for evaluating diverse data sets is that it provides a framework and utilizes objective criteria for assessing causality between exposures to EDCs and selected outcomes (see Chapter 7).
Chapter 2 summarizes critical generic issues (e.g., exposure–outcome associations, dose–response relationships, role of natural hormones and phytoestrogens, etc.), several of which are particularly relevant to EDCs.
Chapter 3 provides background information on the endocrine system, the role of hormones, and potential mechanisms of endocrine disruption along with specific chemical examples of multiple modes of action. The emphasis is on the vertebrate endocrine system and on the hypothalamic-pituitary-gonad, hypothalamic-pituitary-adrenal, and hypothalamic-pituitary-thyroid axes.
Potential adverse outcomes in both wildlife (Chapter 4) and humans (Chapter 5) have focused mainly on reproductive and sexual development and function; altered immune, nervous system, and thyroid function; and hormone-related cancers. Selected data sets illustrating exposure to certain EDCs in different parts of the world are discussed in Chapter 6, along with a discussion of exposure issues particularly relevant to EDCs.
As mentioned, Chapter 7 describes a framework for evaluating the collective information from diverse data sets in a structured manner to provide objective assessments of the state-of-the-science of determining causality between exposures to EDCs and selected outcomes. Chapter 8 summarizes the conclusions and lists some general research recommendations.
Damstra, T; Barlow, S; Bergman, A; Kavlock, R; Van Der Kraak, G
