Endocrine Disrupters - Shaw Flashcards
What is the definition of EDC’s?
An endocrine disrupting chemical (EDC) is an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, its progeny, or (sub)populations.
What are the sources of human exposure to EDC?
EDC come from: plastic bottles or containers, liners of metal food cans, detergents, flame retardants, food, toys, cosmetics, pesticides, etc.
Classes that are well-investigated include: bisphenol A (BPA), phthalates, herbicides, pesticides such as atrazine and DDT, industrial chemicals such as polychlorinated biphenyls (PCBs) and polybrominated diethyl ethers (PBDEs), diethylstilbestrol (DES), dioxins, phytoestrogens, arsenic
What are the mechanisms by which EDC interrupt endocrine pathways?
EDC can act directly as hormone agonists or antagonists that interfere with hormone actions on target cells
EDC can act indirectly by modifying hormone dynamics in circulation, changing hormone metabolism or interfering with hormone regulation
What are the basic characteristics of this class of Endocrine Disrupting Chemicals?
Effective at low doses
Low doses are most effective during development
Non-linear (U-shaped) dose response curve
EDC affinity is not directly related to potency since EDC work together
Tests for EDC must look at life-long follow-ups
Why can’t we really tell if many of these EDCs are truly involved with human health?
A lot of the hormones in the human body work together and it is hard to isolate single functions of one hormone.
How are EDCs involved in various clinical pathologies, such as obesity, diabetes, reproduction, hormone-sensitive cancer and neurodevelopmental disorders?
Disruption of glucose/lipid homeostasis is a risk factor for metabolic disorders including obesity and diabetes mellitus.
How are EDCs involved in various clinical pathologies, such as Diabetes?
In animal models, prenatal and perinatal exposures to EDCs disrupt the homeostatic control of adipogenesis, energy balance and induce obesity.
EDCs alter insulin production, secretion, and/or function, increasing the susceptibility for type 2 diabetes (T2D).
How are EDCs involved in various clinical pathologies, such as reproduction?
EDCs impair key processes in ovarian development in animal models, adversely affect the structure and function of the postnatal ovary by inhibiting follicle growth and/or increasing atresia/apoptosis in animal models, and disrupt steroid hormone levels in animals and women.
EDCs may adversely affect the structure and/or function of the uterus, vagina, and anterior pituitary. EDCs are associated with abnormal puberty, reduced fertility, infertility, polycystic ovarian syndrome, endometriosis, fibroids, preterm birth, and adverse birth outcomes.
Antiandrogens, xenoestrogens, and dioxins are the best-characterized endocrine disruptors of the male reproductive system
How are EDCs involved in various clinical pathologies, such as hormone-sensitive cancer in women?
EDCs => alter mammary development, susceptibility to tumors and lactation after critical period exposures.
Dioxin early life exposure leads to delayed pubertal breast tissue development in female rodents and in girls. Dioxin also has demonstrated effects on later life lactation and breast and ovarian cancer risk.
How are EDCs involved in various clinical pathologies, such as neurodevelopmental disorders?
The mechanism of EDC actions in the brain include molecular and cellular changes in expression of genes and proteins involved in neuroendocrine and other behaviors, including cognitive and affective functions.
The brain is highly vulnerable to EDC exposure because of the widespread distribution of hormone receptors, enzymes and neurotransmitter systems on which EDCs can act.
How are EDCs involved in various clinical pathologies, such as hormone-sensitive cancer in men?
A number of EDCs have been associated with aberrant prostate growth.
EDC classes with known prostatic effects include pesticides, PCBs and BPA.
Epidemiological evidence indicates increased prostate cancer rates and mortality in men exposed to specific pesticides, PCBs, and inorganic arsenic.
