NURS 735 - APPLIED TOXICOLOGY

To guide your understanding of key concepts throughout this module on d endocrine disrupting chemicals, please read the following reading materials. The hyperlink below refers you to a chapter from "Generations at Risk," and focuses on Endocrine Disrupting Compounds (EDCs) and their varied effects on humans and the environment. This is a pdf file and may take some time to print. Since some computers have long download and print times, please download the file to your hard drive first, and then print it (that way you are not online for extended periods just for the sake of printing...). Also, read the abstract (Overview and Background on EDCs) from Servos et al., anchored below on this page.

Overview of Endocrine Disruption (Flash presentation by guest contributor, Dr. Jodi Flaws)

Effects of Endocrine Disruption in Womens' Health (QuickTime movie and figures presented by Dr. Jodi Flaws)

Effects of Endocrine Disrupting Compounds (Overview from: Generations at Risk):

Define what constitutes an endocrine disrupting compound.
Understand three mechanisms by which EDCs interfere with normal hormone function.
Describe different types of effects of EDC exposure in humans and animals

Overview and Background Information on Endocrine Disrupting Compounds.

Abstracted from "Scientific Assessment of Endocrine Disrupting Substances in the Canadian Environment," by Mark Servos, Glen J. Van Der Kraak, and Michael Wade
Water Quality Research Journal of Canada, 36(2): 171-173 (2001)

With the publication of Silent Spring in the early 1960s, Rachel Carson drew public attention to the reproductive and developmental effects in wildlife associated with the widespread use of persistent pesticides and other industrial chemicals. Considerable effort over the past several decades has significantly reduced the exposure of humans and cosystems to these persistent contaminants. However, the recent publication of Our Stolen Future, by Colborn et al. in 1996, once again heightened public awareness that very low concentrations of environmental contaminants could potentially result in adverse effects on reproduction and development in humans and wildlife. Contaminants that can alter the normal function of endocrine systems, especially during critical periods of development, could lead to irreversible effects in the organism or its offspring. These concerns have led governments worldwide to reevaluate the approaches to assessing and managing substances with the potential to disrupt endocrine function. This is being done in order to develop a better understanding of the exposure and hazard associated with endocrine disrupting substances (EDS) and to reduce the uncertainty associated with assessing their risk to human health and the environment.

Endocrine systems coordinate and regulate internal communication in cellular organisms. Endocrine cells release chemical messengers, known as hormones, which are carried into contact with target cells in the body. Interactions between the hormone and particular recognition features (receptors) in the cell, trigger pre-existing cellular responses that may result in effects on growth, development, or reproduction, as well as numerous other critical biological functions. The endocrine system can be adversely affected by a wide variety of substances that interact with specific receptors and alter the cells? ability to control physiological processes. A substance can act like a hormone by binding to a receptor and causing a response (agonistic response) or it can bind to a receptor and prevent a normal response (antagonistic response). In addition, a substance might interfere with the synthesis, transport or metabolism of hormones or receptors. To date, most of the attention has been on substances that mimic or block the feminizing effects of the estrogens such as 17b-estradiol. However, substances can also affect other sex hormones (androgens or progestins) or other endocrine systems, such as the pituitary or thyroid, which influence growth, development and behaviour. Not surprisingly, the mechanisms by which substances disrupt endocrine systems can be very complex and are currently not fully understood.

There is growing evidence that chemicals may have effects on reproduction and development of humans and ecosystems. Although most of the information is circumstantial, a growing body of evidence throughout the industrialized world suggests that a variety of effects, such as increasing incidence of specific cancers, decreased sperm counts, and potential impaired cognitive development, are related to exposure to environmental contaminants. The most compelling evidence for the effects of EDS comes from studies showing that the growth, reproduction and development of many species of invertebrates, fish, reptiles, birds and mammals, can be impacted by substances that interact with endocrine systems. Many of these chemicals have the ability to cause biological responses at the very low levels commonly found in the Canadian environment. The significance of these chemicals to human health and the sustainability of ecosystems are currently the focus of considerable public concern, scientific research and debate.

Considering the complexity of endocrine systems, it is not surprising that the range of substances reported to cause endocrine disruption is diverse, and includes both natural and synthetic chemicals. Synthetic chemicals of concern include those that may be released intentionally (such as pesticides), as by-products of industrial processes and waste disposal (such as dioxins or PCBs), or discharged from industrial or municipal treatment systems (such as alkylphenols). Biota in the environment can also be exposed to unusually high concentrations of natural substances, such as phytoestrogens or sex hormones, as a result of industrial, agricultural or municipal waste practices. The wide variety of substances and sources of endocrine disrupting substances presents an enormous challenge to environmental managers in both industry and government.

Until recently, much of the research on endocrine disrupting substances was focused on persistent, bioaccumulating, toxic substances, such as PCBs, dioxins and some organochlorine pesticides. Many of these chemicals remain widely distributed in the environment even though their manufacture and use have been curtailed or banned in Canada. However, the EDS issue has focused attention on a number of substances and effluents that are not highly persistent, but are widespread in the environment and that can exert effects at relatively low levels. Effects on growth, reproduction and development of organisms in Canadian ecosystems have been associated with pulp mill, industrial and municipal effluents, agricultural runoff and with specific chemicals such as alkylphenols, tributyltin, and numerous pesticides. Although reproduction and development have been, and continue to be major endpoints for the toxicological assessment of substances, the EDS issue has heightened concerns for detecting biological effects mediated through endocrine systems. The subtle nature of many of the observed effects on growth, development, reproduction or neurodevelopment makes them very difficult to detect. Of particular concern is the knowledge that minor alterations of endocrine function during critical life stages may have significant impacts on the performance of individuals. Many of the tools and approaches used in the past to detect or assess the impacts of toxic chemicals may be inadequate to detect the subtle impacts on endocrine function. Several major international efforts (e.g., OECD, U.S. EPA) have been initiated to develop screening and testing protocols for EDS. There remains considerable uncertainty associated with interpretation of endocrine mediated responses in biota. How individual agencies and governments will interpret and apply the rapidly growing body of knowledge on EDS within regulatory programs is uncertain. However, it has been recognized that governments must be proactive so that the uncertainty is reduced and regulatory decisions on EDS are based on the best available science.

Because the types of substances that may alter endocrine function are so diverse, the EDS issue influences many other national and international programs related to the assessment and management of toxic chemicals, including Children's Environmental Health, Persistent Organic Pollutants (POPs), Environmental Effect Monitoring, New Substances, safety of medical devices or consumer products, Priority Substances, and pesticide registration and regulation. The complexity and potential magnitude of the EDS issue will require a coordinated response among government agencies, universities, industry and the public.

Assignment:

Homework:

Through your readings and other literature that you obtain, provide a list of candidate EDC chemicals that can be found currently in our environment. Which exposure-related effects would most likely show up in a community that you might work with? Please post your responses to these questions on the Discussion Board.

Not assigned:

Toxic Chemicals & Health: Health Threats & Effects: In Depth: Technical Brief (Natural Resources Defense Council)

Water Quality Research Journal of Canada, 36(2): 253-271 (2001) (abstract only; email author for e-reprint)

Endocrine Disruption in Fish: An Assessment of Recent Research and Results

Water Quality Research Journal of Canada, 36(2): 253-271 (2001)
Endocrine Disruption and Human Reproductive Effects: An Overview
Warren G. Foster*

Normal Brain Development and Developmental Toxicology (In Harm's Way, Chapter 2)

Neurodevelopmental Toxicology (In Harm's Way, chapter 6)

Effects of Endocrine Disrupting Compounds (Generations at Risk)