Introduction

LINDA VIKSTRÖM BERGANDER AND INGEMAR PONGRATZ

Department of Biosciences and Nutrition, Karolinska Institute, SE-141 83 Huddinge, Sweden

1.1 General Introduction

Food consumption is a global issue involving a complex chain of food producers, food handling, transporting and packaging, among others. Today, there is a substantial knowledge of the various hazards ending up in foodstuffs. These hazards range from simple physical hazards to biological hazards, including pathogenic bacteria and naturally occurring toxins, as well as chemical hazards such as pesticides and heavy metals. There is a large heterogeneous group of compounds present, both naturally and man made, in the environment that is causing adverse health effects. These chemical compounds that disturb hormonal pathways are often known as endocrine disrupting chemicals (EDCs).

Exposure to chemical contaminations from the diet is the main critical route for humans, as well as wildlife, to persistent bioaccumulative (fat-soluble compounds with a tendency to build up and reach high levels in an organism) EDCs. Basically, the hormonal or endocrine disruptors are chemicals with the potential to interfere with the function of endocrine systems. Thus, this book will be focusing on diet-derived hazardous substances that disturb/influence nuclear receptor signaling and thereby target the hormonal systems.

1.1.1 Endocrine Disruptive Chemicals

Environmental pollutants and their effects on the environment, humans and animals are a significant concern in today's society. During recent years there has been substantial awareness that a variety of environmental pollutants can intervene with the hormonal system. Many man-introduced compounds influence the hormonal system of animals and may be responsible for developmental and reproductive abnormalities seen in wildlife. Natural sources of EDCs are present in various types of foods and are susceptible to metabolic degradation; however, synthetic industrial chemicals, such as inorganic contaminants, agrochemicals, industrial chemicals, plasticizers, plastics, and pharmaceutical agents, that leak into the soil, have the ability to end up in the food chain and thereby bioaccumulate in animals and humans.

The term endocrine disruptor was evolved at the Wingfield meeting in 1991, where a group of researchers with diverse backgrounds was united to discuss the effects of mammalian exposure to environmental chemicals. As a result of the meeting, a consensus statement was set by the participants: "We are certain of the following: a large number of man-made chemicals that have been released into the environment, as well as a few natural ones, have the potential to disrupt the endocrine system of animals, including humans". It was also concluded that the effects of such chemicals are diverse when comparing embryo, fetus, and perinatal organisms to adults and that detectable effects are commonly seen solely in the offspring. Later on, the so-called "endocrine disruptor hypothesis" was published in the book Our Stolen Future, which essentially claimed that certain synthetic chemicals interfere with hormone synthesis and, thus, disrupt endocrine networks in animals and humans. To clarify the concept of EDCs, the U.S. Environmental Protection Agency (EPA) defined EDCs as "exogenous agents that interfere with the production, release, transport, metabolism, binding action, or elimination of the natural hormones in the body, responsible for the maintenance of homeostasis reproduction and the regulation of developmental processes".

In 1962, prior to the Wingfield meeting, Rachel Carlson wrote the alarming book Silent Spring. This groundbreaking book recapitulates a small fictional world on the road to ruin as a result of accumulated separate disasters; how- ever, all were picked from real life. She discussed the widespread use and the danger of environmental chemicals, such as pesticides and herbicides, on wildlife development and reproduction. This warning for man-made chemicals was first of a kind and, hence, a precursor to the debates on the use of chemical pesticides that later on would result in a ban of the heavily used insecticide DDT, as well as polychlorinated biphenyls (PCBs) in the USA.

1.1.2 Biological Pathways Affected by EDCs

The scientific community has become increasingly concerned that humans experience health problems and wildlife populations are adversely affected following exposure to chemicals that interact with the endocrine system. A well functioning endocrine system, a hormonal balance, is a central function and a key issue for maintaining physiological homeostasis and a healthy body. One hormone in imbalance affects other hormones in the body.

The basics of the endocrine system are a number of glands that secrete the chemical messages that we call hormones. The major glands of the endocrine system are the hypothalamus, pituitary, thyroid, parathyroid, adrenal, pineal body, and the reproductive organs (ovaries and testes). These glands release a diversity of hormones directly into the bloodstream, where they target an organ and thereby regulate various processes, like growth, metabolism, development, reproduction, and sexual characteristics.

Hormones exert their action through a range of receptors by a lock-and-key model. These receptors are either (i) membrane bound and linked to ion channels, G-proteins, or enzymes or (ii) intracellular and localized in the nucleus or the cytosol. The membrane-bound receptors mediate the cellular response to hormones either by a depolarization of the membrane or by the generation of so-called second messengers or signal...