Endocrine disruptors, also referred to as endocrine disrupting chemicals (EDCs), are compounds that interfere with the normal actions of hormones, often by mimicking or blocking the actions of these endogenous signaling molecules. Endocrine disruptors have many important features, including their ability to act at low doses, to inflict greater damage when exposures occur during critical windows of development, and to disobey the traditional response where the “dose makes the poison,” for example, greatest harm is often not seen at the highest doses. Harm to both human and wildlife populations has been documented after exposures to endocrine disruptors, although limitations in epidemiological and other observational study designs have often made it difficult to draw causal inferences. Instead, laboratory animal studies have been used to study many common endocrine disruptors and to better understand the mechanisms by which these chemicals act. Yet, limitations in how animal and cell culture studies are used have led to concerns that risk assessments, conducted by regulatory agencies charged with protecting public health, are failing to predict harm from exposures. For this reason, scientists studying endocrine disruptors have challenged the traditional methods by which “safe” doses of exposure to hazardous chemicals are determined, suggesting that these methods do not work for endocrine disruptors and perhaps are also flawed for other environmental exposures. Since the 1990s our understanding of endocrine disruption has blossomed, and researchers from many scientific disciplines have contributed to the study of these chemicals, including attempts to avoid replacing them with regrettable substitutions.
In the mid-1900s, industrialization of synthetic chemical manufacturing and the use of these chemicals in consumer products became popular and common. The use of chemicals in everyday products brought ease and comfort to a growing and fast-paced society. The publication of Rachel Carson’s Silent Spring, in which she discussed the adverse effects of the pesticide DDT and other widely used chemicals, sparked the environmental movement and a sense of awareness of the threat that these chemicals could pose to the world (Carson 1962). Although work by environmental health scientists and ecologists built on the work of Carson and others, it was not until 1991 that the focus on the effects of these chemicals on the endocrine system gained widespread attention. At that time, scientists from interdisciplinary fields met at the Wingspread Conference Center in Racine, Wisconsin, to discuss the effects of hormonally active environmental chemicals on humans, laboratory animals, and wildlife. These scientists concluded in the publication of Colborn, et al. 1993 that synthetic chemicals, as well as some natural chemicals, were capable of altering the function of the endocrine system. It was at this conference that the term “endocrine disruptor” was coined. Since the 1990s research has identified dozens, if not hundreds, of endocrine disruptors and their effects on laboratory animals, humans, and wildlife populations. This work is excellently reviewed in Bergman, et al. 2013 and Gore, et al. 2015. Vandenberg and colleagues have addressed additional important topics that are relevant to endocrine disruptors and that have been uncovered and examined, including concepts of “low dose effects” and “non-monotonic dose responses” in publications that include Vandenberg 2014; Vandenberg, et al. 2012; and Vandenberg, et al. 2013. Furthermore, Barouki, et al. 2012 and Heindel, et al. 2015 address the important concept of “developmental origins of health and disease.”
Barouki, R., P. D. Gluckman, P. Grandjean, M. Hanson, and J. J. Heindel. 2012. Developmental origins of non-communicable disease: Implications for research and public health. Environmental Health 11:42.
Provides an excellent overview of the changes in prevalence of non-communicable diseases and the known associations between these diseases and environmental chemicals. This review mostly focuses on diseases that are thought to be “triggered” in some way during early development, even though they typically manifest in adulthood.
Bergman, Å, J. J. Heindel, S. Jobling, K. A. Kidd, and R. T. Zoeller, eds. 2013. The state-of-the-science of endocrine disrupting chemicals— 2012. Geneva, Switzerland: United Nations Environment Programme and World Health Organization.
This is a “state of the science” document summarizing the knowledge about endocrine disruptors up to the date of publication. Supported by the United Nations Environment Programme and the World Health Organization, this document is split into subsections that describe general knowledge about endocrine disruptors, evidence for their effects on humans and wildlife, and known exposure sources.
Carson, R. 1962. Silent spring. New York: Houghton Mifflin.
Although Rachel Carson’s seminal book on environmental chemicals did not specifically address endocrine disruptors (they were not yet identified as such at the time of her writing), her book discusses numerous chemicals that are now known to interfere with hormone action.
Colborn, T., F. S. vom Saal, and A. M. Soto. 1993. Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environmental Health Perspectives 101.5: 378–384.
This is a classic paper important in the launching of the study of endocrine disruptors. The authors review what was known at the time about the influence of environmental chemicals on the endocrine system and the known impacts of those chemicals on human and wildlife populations.
Gore, A. C., V. A. Chappell, S. E. Fenton, et al. 2015. Executive summary to EDC-2: The Endocrine Society’s second scientific statement on endocrine-disrupting chemicals. Endocrine Reviews 36.6: E1–E150.
This manuscript offers an extremely comprehensive review of the field of endocrine disruption. Written by experts affiliated with the Endocrine Society, the review breaks down its analyses by organ systems (e.g., male reproduction, female reproduction, brain, metabolic organs, etc.).
Heindel, J. J., J. Balbus, L. Birnbaum, et al. 2015. Developmental origins of health and disease: Integrating environmental influences. Endocrinology 156.10: 3416–3421.
Another important manuscript that describes the connection between health during early life and disease incidence in later life, with a focus on environmental influences, including endocrine disruptors.
Vandenberg, L. N. 2014. Low-dose effects of hormones and endocrine disruptors. Vitamins & Hormones 94:129–165.
Examines the concept of “low dose effects,” which has received significant attention in recent years from researchers and regulators trying to evaluate the safety of endocrine disruptors.
Vandenberg, L. N., T. Colborn, T. B. Hayes, et al. 2012. Hormones and endocrine-disrupting chemicals: Low-dose effects and nonmonotonic dose responses. Endocrine Reviews 33.3: 378–455.
This comprehensive review examines the concept of “low dose effects” and also the issue of “non-monotonic dose responses.” These have been considered controversial topics, but they are integral to understanding the science of hormones and endocrine disruptors. This manuscript provides dozens of examples of each phenomena.
Vandenberg, L. N., S. Ehrlich, S. M. Belcher, et al. 2013. Low dose effects of Bisphenol A: An integrated review of in vitro, laboratory animal and epidemiology studies. Endocrine Disruptors 1.1: e26490.
Bisphenol A (BPA) is one of the best-studied endocrine disruptors. This manuscript reviews the evidence from a range of different study designs, including cultured cells, laboratory animals, human populations, and wildlife, to demonstrate that BPA induces adverse effects at low doses.
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