What Are Endocrine Disrupters and Where Are They Found?

Philippa D. Darbre

This chapter provides an introduction to the importance of hormones to the healthy functioning of the human body and an overview of the varied types and sources of environmental chemicals that can interfere in their action. Such compounds, termed endocrine-disrupting chemicals (EDCs), may occur naturally, but the majority are artificial compounds that have been released into the environment without prior knowledge of their impact on human health. The chapter begins with some historical background, especially related to the endocrine-disrupting effects of EDCs in wildlife, and then outlines general mechanisms by which EDCs may disrupt hormone activity. Descriptions are then given of the range of compounds that are EDCs, their chemical structures, and the sources of exposure for the human population.

Keywords

Alkylphenol; bisphenol A; endocrine disrupter; hormone; hormone receptor; mycoestrogen; organometals; persistent organic pollutants; personal care products; phthalate; phytoestrogen; steroid

Outline

1.1 Introduction

Human health depends on a functional endocrine system in which hormones act as chemical messengers to regulate and coordinate bodily functions. The hormones are secreted by glands distributed around the body and are then carried by the blood to act on cells of distant target organs. Their ability to act at the target organs is determined by binding to specific cellular receptors, which then relay signals to the target cells. The healthy functioning of the human body depends on the coordinated actions of a balanced network of hormones, each at the correct concentration and all acting in synchrony with one another at exactly the appropriate times. It is now recognized that many chemicals present in the environment have the ability to interfere in the action of human hormones and therefore are termed endocrine-disrupting chemicals (EDCs). They can act to disrupt the balance and coordination of the normal homeostatic processes of hormone activity. Some of these compounds are present in nature, but the majority are artificial and released into the environment by the activities of humans without any prior knowledge of their impact on ecosystems, animal welfare, or human health. Therefore, there is now the potential for long-term harm to human health. This book will seek to provide the current state of evidence linking exposure to EDCs with specific human health issues.

1.2 Historical Background

Although endocrine disruption has been receiving high-profile attention only since the 1990s, the phenomenon has been known for considerably longer than that (Figure 1.1). In the 1920s, pig farmers in the United States became concerned about the lack of fertility in swine herds fed with moldy grain [2]; this was exacerbated in the 1940s, when sheep farmers in Western Australia reported infertility in their sheep after grazing on specific fields of clover [3]. More recent research has showed that the underlying reasons were consumption of estrogenic compounds contained within the mold (mycoestrogens) or plant material (phytoestrogens), which were disrupting fertility through their potent estrogenic activity.

In the 1950s, chemists in London led by Sir Charles Dodds were synthesizing a range of chemicals with estrogenic properties [4] for the purpose of studying the mechanisms of estrogen action. Therefore, a potential medical value of such compounds was realized [5] and a new industry of synthetic hormones was born, ultimately leading to the development of oral contraceptives and hormone replacement therapy. The 1950s and 1960s heralded a new culture of sexual freedom, and oral contraceptives were widely adopted as a result. As this same generation grew older, these women wanted to control menopausal symptoms as well, and hormone replacement therapy became a normal expectation of the population as a whole. The long-term consequences of the desire to control reproductive hormone exposures have still to be fully understood, in terms not only of effects on the individual person, but also of the consequences of releasing so many synthetic hormones and their metabolites into the environment.

In 1962, the book Silent Spring by Rachel Carson was published [6], warning of the long-term consequences of environmental contamination with artificial chemicals, most notably from the liberal agricultural use of pesticides and herbicides. She described the already evident loss of wildlife from chemical contamination of the land and predicted worse to come if chemical use continued to increase unchecked. In the following decades, endocrine-disrupting properties of the pesticide dichlorodiphenyltrichloroethane (DDT) and its metabolites were reported in birds [7] and mammals [8,9], which coincided with controversial warnings of more widespread consequences of pollution for wildlife populations from organochlorine compounds. Carson died in 1964, so she never lived to see that the impact of her book sparked an international environmental movement to champion the issues raised. The book Our Stolen Future was published by Theo Colborn and colleagues in 1996, and it is considered a follow-up publication describing even more serious environmental warnings [10]. Many questioned whether the effects reported in wildlife might be predictive of the impending effects on human health, but the scope of the proof needed for invoking any precautionary principle was an immense scientific and clinical task.

This concern led to meetings to discuss the issues, the first of which was the World Wildlife Fund (WWF) Wingspread Conference in Wisconsin in the United States in 1991. Here, the term endocrine disrupter was first proposed, and the consensus statement published the next year was insightful and still relevant today [11] and has been built on over the past 15 years [12]. In Europe, the Weybridge Meeting in 1996 reported similar findings [1] and again has been built on over the past 15 years [13]. Other countries, including Australia, South Korea, and Japan, held similar meetings [12]. In 2009, following 18 years of research after the Wingspread meeting, a scientific statement was published by the Endocrine Society of the United States that outlined the mechanisms and effects of endocrine disrupters and showed how experimental and epidemiological studies converge with human clinical observations “to implicate EDCs as a significant concern to public health” [14]. In 2013, the World Health Organization (WHO) and the United Nations Environment Programme (UNEP) released a study (the most comprehensive report on EDCs to date) calling for more research to fully understand the association between EDCs and the risks to health of human and animal life [15]. CHEM Trust has collated an annotated list of key scientific statements on EDCs between 1991 and 2013, which provides more useful chronological information and is accessible online [16].

In 1998, the US Environment Protection Agency (EPA) announced the Endocrine Disrupter Screening Program, which was given a mandate under the Food Quality Protection Act and Safe Drinking Water Act to establish a framework for priority setting, screening, and testing of more than 85,000 chemicals in commerce. The basic concept behind the program was that prioritization would be based on existing information about chemical uses, production volume, structure...